The progressive histological differentiation of the thyroid gland of the horse

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Content THE PROGRESSIVE HISTOLOGICAl RIFFEREHTIATIOH
OF THE THYROID GLAND
OF THE HORSE
A T h e s is
P r e s e n t e d to
th e F a c u lt y o f t h e D epartm ent o f Zoology
U n i v e r s i t y o f S o u th e rn C a l i f o r n i a
In P a r t i a l F u l f i l l m e n t
o f t h e R e q u ire m e n ts f o r th e D egree
M a ste r o f S c ie n c e i n Zoology
“ by
Eva Brooks
May 1937
U M I Number: EP67098
All rights reserved
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This thesis, written by
EVA BROOKS
under the direction of h£JL- Faculty Committee,
and approved by all its members, has been
presented to and accepted by the Council on
Graduate Study and Research in partial fulfill
ment of the requirements for the degree of
MASTER OF SCIENCE
Secretary
Date Ju ne ^...1 9 . 5 . . ? . . . . .
Dean
Faculty Committee
Chairman
TABLE OF CONTENTS
CHAPTER PAGE
I . INTRODUCTION.................................................................................... 1
I I . REVIEW OF LITERATURE.............................................................. 3
I I I . MATERIALS AND M ETHOD S......................................................... 10
IV. OBSERVATIONS AND FINDINGS
E a rly D e v e l o p m e n t ........................................... 14
5-mm. E m b r y o .......................................................... 14
6-mm. E m b r y o .......................................................... 15
9-mm. E m b r y o .......................................................... 16
13-mm. E m b r y o ............................................... 17
1 4 . 5-mm. E m b r y o ............................................... 18
16-mm. Embryo .......................................................... 19
lB-19-mm. Embryo ...................................... 22
21-mm. E m b r y o ......................................................... 2Z
30-mm. Embryo ...................................... 26
35-mm. E m b r y o ........................................................... 27
55-mm. E m b r y o .......................................................... 29
64-117-mm. E m b r y o .......................................................... 31
158-mm. Embryo ........................................................... 34
180-230-mm. Embryo ..................................................... 35
A d u lt H o r s e .......................................................... 37
V. DISCUSSION...................................... 40
V I. SUMMARY............................................................................................. 52
V I I . BIBLIOGRAPHY.................................................................................. 54
I . INTRODUCTION
M u l t ip l e i n v e s t i g a t i o n s have b een made on th e o r i g i n
and d i f f e r e n t i a t i o n o f t h e t h y r o i d g la n d in d i f f e r e n t v e r t e
b r a t e s , some o f th e p u b l i c a t i o n s d a t i n g b a ck to th e e a r l y
p a r t o f th e n i n e t e e n t h c e n t u r y . Much o f t h i s s tu d y was
d i r e c t e d to th e d e r i v a t i o n and m orph o g en esis o f th e f o l l i c l e ,
w h ile a more l i m i t e d number c o n c e rn e d th e p r e f o l l i c u l a r p e r i
od. N o r r i s { ’1 6, ’18) made a s y s te m a tic and co m p lete a r r a n g e
ment o f th e d e v e lo p m e n ta l s t a g e s o f th e human t h y r o i d g la n d
from i t s g e n e s i s u n t i l m a t u r i t y . The w r i t e r h a s b e en u n a b le
to f i n d any r e p o r t o f i n v e s t i g a t i o n s c o n c e rn in g th e p r o g r e s
s i v e , h i s t o l o g i c a l d i f f e r e n t i a t i o n o f th e t h y r o i d g la n d in
th e h o r s e d u r i n g p r e n a t a l l i f e . Arx ( ’ 2 8 ), in a d i s s e r t a
t i o n a t th e U n i v e r s i t y o f B e rn , h a s g iv e n a th o ro u g h and d e
t a i l e d a c c o u n t o f th e s t r u c t u r e and d e v e lo p m e n ta l c h an g es o f
th e g la n d from th e tim e o f b i r t h , f o r each y e a r , u n t i l o ld
a g e . In th e p r e s e n t i n v e s t i g a t i o n an a tte m p t h a s b e e n made
t o t r a c e th e e a r l y d e v e lo p m e n ta l s t a g e s , and to compare
t h e s e s t a g e s w ith th o s e i n th e human and in o t h e r v e r t e
b r a t e s , in t h e hope t h a t a c o n t r i b u t i o n o f some v a lu e may
be added to th e i n f o r m a tio n a l r e a d y a c c u m u la te d .
T h is i n v e s t i g a t i o n h a s b e e n c a r r i e d on u n d e r th e
d i r e c t i o n o f Dr. B. H. H a r r is o n to whom th e a u th o r i s i n
d e b te d f o r t h e s u g g e s tio n o f t h e p ro b lem . H is v a l u a b l e
2
a s s i s t a n c e and h i s i n t e r e s t and e n th u s ia s m hav e been con
s t a n t s o u r c e s o f i n s p i r a t i o n and e n co u rag e m en t.
The a u th o r a l s o w ish e s to e x p r e s s h e a r t y th a n k s to
t h e o t h e r members o f th e c o m m ittee , D r. G. R. J o h n s to n e , and
D r. F. M. B aldw in f o r t h e i r c o n s u l t a t i o n ; to Dr. D. B. Mac-
Callum f o r h i s a i d on h i s t o l o g i c a l s t r u c t u r e s ; to Mr. and
Mrs. P a u l L. M o ts in g e r f o r t h e i r h e lp i n c o l l e c t i n g and p r e
p a r i n g m a t e r i a l s ; and to Mr. Aaron J e n s e n and Mr. E a r l G.
B a ird f o r p h o to g ra p h in g i l l u s t r a t i o n s .
I I . REVIEW OF LITERATURE
The l i t e r a t u r e s e t t i n g f o r t h t h e f i n d i n g s o f numerous
i n v e s t i g a t o r s o f th e t h y r o i d g la n d i s so e x t e n s i v e t h a t no
a tte m p t w i l l he made to re v ie w th e e a r l i e r p u b l i c a t i o n s .
Only th e o u t s t a n d i n g ones o f th e l a s t t w e n t y - f i v e to t h i r t y
y e a r s w i l l be in c l u d e d .
T here h a s b e en c o n s i d e r a b l e c o n tr o v e r s y a s to w heth
e r th e t h y r o i d g la n d i s d e r i v e d from a s i n g l e m edian, v en
t r a l so u rc e o r from t h i s m edian a n la g e combined w ith two o f
a l a t e r a l o r i g i n , w hich w ere known in e a r l i e r w r i t i n g a s
" l a t e r a l t h y r o i d a n la g e n " and l a t e r a s " u l ti m o b r a n c h ia l
b o d i e s . " M arine ( ’32) h a s g iv e n a c o m p reh en siv e re v ie w o f
th e f i n d i n g s and c o n c l u s i o n s o f num erous i n v e s t i g a t o r s work
in g to d e te rm in e t h i s e m b ry o lo g ic a l o r i g i n . The t h y r o i d
g la n d s o f a l l c l a s s e s o f v e r t e b r a t e s i n c l u d i n g many d i f f e r e n t
mammals have b e e n s t u d i e d . M arine s t a t e s t h a t t h e r e re m a in s
no lo n g e r any d o u b t a s to th e s i n g l e , m edian o r i g i n . He s a y s ,
"The e v id e n c e b r o u g h t fo rw a rd d u r in g th e l a s t tv æ n ty y e a r s
h a s a p p a r e n t l y c l e a r e d up t h e c o n tr o v e r s y and e s t a b l i s h e d th e
u n i f o r m i t y o f th e o r i g i n o f t h i s g la n d th r o u g h o u t a l l v e r t e
b r a t e s . " W e lle r ( ’31) r e v i v e s th e te rm " l a t e r a l t h y r o i d "
f o r u l t i m o b r a n c h i a l body i n t h e human w ith s p e c u l a t i o n t h a t
" i t i s endowed w i t h t h y r o i d fo rm in g p o t e n c i e s . " K ing sb u ry
(3 5 a) f i n d s no e v id e n c e to s u p p o rt t h i s c o n c l u s i o n . Godwin
4
(37) in h i s stu d y o f th e t h y r o i d o f t h e dog f i n d s t h a t th e
n i t i m o b r a n c h i a l body becomes i n c o r p o r a t e d w i t h i n t h e t h y
r o i d t i s s u e and " t h a t i t does form t h y r o i d t i s s u e by in d u c
t i o n . "
The e a r l y developm ent o f t h e g la n d i n th e human,
from th e tim e i t o r i g i n a t e s u n t i l th e p e r io d o f th e f o r m a tio n
o f p rim a ry f o l l i c l e s , h a s been a b ly i n v e s t i g a t e d by N o r r i s
( ’1 8 ) . He f i n d s t h a t th e p r i m o r d i a l p l a t e o f e a r l y embryos
i s b ro k e n up i n t o p l a t e s o r b a n d s two c e l l s in t h i c k n e s s ,
by a system o f i n t r a g i a n d u la r c a v i t i e s . From t h e s e p l a t e s
th e p rim a ry f o l l i c l e s d e v e lo p . In a c a s u a l stu d y o f o t h e r
a n im a ls — p ig e o n , dog, p i g , s h e e p , and r a b b i t — he f i n d s th e
same f e a t u r e in th e m o rp h o g en e sis o f th e g l a n d . Bradway
( ’ 2 9 ), i n h e r s tu d y o f th e c h ic k t h y r o i d , c o n firm s th e o r i
g i n o f f o l l i c l e s d e s c r i b e d by N o r r i s ( ’1 6 ) . They a r i s e
from a c o i l e d , f e n e s t r a t e d membrane two c e l l s t h i c k . Godwin
( ’ 37) i s u n a b le to c o n fir m t h e s e f i n d i n g s in th e d og . He
o b s e r v e s a r a t h e r complex b r a n c h in g from th e o r i g i n a l t h y
r o i d p l a t e .
The o r i g i n and form o f th e t h y r o i d f o l l i c l e h a s
b e en a s u b j e c t o f i n v e s t i g a t i o n by many r e s e a r c h w o rk e rs
from th e tim e when J o n e s (1836) d e s c r i b e s th e t h y r o i d f o l
l i c l e s a s c o m p le te ly c lo s e d v e s i c l e s , to th e p r e s e n t tim e .
The r e a d e r i s r e f e r r e d to th e p u b l i c a t i o n by N o r r i s ( ’16)
f o r a co m p lete c h r o n o l o g i c a l r e v ie w o f a l l l i t e r a t u r e d e a l -
in g w i t h th e human t h y r o i d f o l l i c l e and some o b s e r v a t i o n s
on lo w e r fo rm s to th e tim e o f h i s p u b l i c a t i o n . N o r r i s b e
l i e v e s t h a t p rim a ry f o l l i c l e s d e v e lo p d i r e c t l y from f e n e s
t r a t e d , e p i t h e l i a l p l a t e s , two c e l l s in t h i c k n e s s , by r e
a rra n g e m e n t o f th e c e l l s , c e l l p r o l i f e r a t i o n , i n c r e a s e in
s i z e o f c e l l s , and lumen f o r m a t io n . Secondary f o l l i c l e s
d e v e lo p from p r e - e x i s t i n g f o l l i c l e s by s o l i d b u d s , by h o l
low b u d s , o r by c o n s t r i c t i o n o f th e p a r e n t f o l l i c l e .
W illia m so n and P e a r s e ( ’23) d e s c r i b e th e f u n c t i o n a l u n i t
o f th e t h y r o i d g la n d a s a l o n g , c y l i n d r i c a l column o f e p i
th e liu m u s u a l l y t w i s t e d , enmeshed in a p le x u s o f c a p i l l a r i e s ,
and f l o a t i n g w i t h i n a ly m p h a tic s y n u s o id . M arine ( ’32)
s t a t e s t h a t i n r e g e n e r a t i o n , new f o l l i c l e s a r e form ed on
demand th ro u g h th e d i f f e r e n t i a t i o n o f sm all f o l l i c l e s and
u n d i f f e r e n t i a t e d t h y r o i d c e l l s l y i n g b etw een th e l a r g e r f o l
l i c l e s . These sm a ll f o l l i c l e s and i n t e r f o l l i c u l a r c e l l s , he
c la im s , a r e num erous d u r in g l a t e f e t a l l i f e and in f a n c y and
a r e c o n s i d e r e d a s new f o l l i c l e s o r buds in v a r i o u s s t a g e s
o f d e v elo p m en t d u r in g a p e r i o d o f r a p i d g ro w th . They d e
c r e a s e w ith age u n l e s s th e g la n d h a s an abnorm al grow th s t i
m u la tio n .
Many have c o n t r i b u t e d to o u r knowledge o f th e shape
and s i z e o f f o l l i c l e s , b u t o n ly a few o f th e more o u t s t a n d
in g w i l l be m e n tio n e d . A s c h o ff ( ’24) b e l i e v e s t h e r e i s a
d i f f e r e n c e betw een th e f o l l i c l e s o f th e c e n t r a l and o f th e
6
p e r i p h e r a l r e g i o n s . The c e n t r a l f o l l i c l e s , he c la im s , a re
more i r r e g u l a r and o f t e n e lo n g a te d . Even b r a n c h in g form s
may be found t h e r e . He c a l l s them " c e n t r a l c a n a l i c u l i . "
W ilson ( ’ 2 7 - ’28) h a s v i s u a l i z e d th e f o l l i c l e s in th e norm al
and p a t h o l o g i c a l human t h y r o i d by a method o f wax r e c o n
s t r u c t i o n s . He d e m o n s tr a te d th e sh a p e , s i z e , and s p a t i a l
r e l a t i o n s h i p o f t h e f o l l i c l e s . A cco rd in g to h i s f i n d i n g s
th e norm al t h y r o i d f o l l i c l e s a r e ro u n d , o v a l, o r b ra n c h e d ,
and r a n g e from 150-300 m ic ro n s in d i a m e t e r . He c o n firm s
N o r r i s ’ e x p la n a t i o n on b u d d in g b u t b e l i e v e s d i v i s i o n h a s a
r a t h e r i n f e r i o r and i n s i g n i f i c a n t p la c e i n t h e norm al a d u l t
g l a n d , thou gh i t does o c c u r in th e f o e t u s . He b e l i e v e s i n -
t e r f o l l i c u l a r t i s s u e i s m e re ly th e t i p end o f a sm a ll o r
new f o l l i c l e , due to t a n g e n t i a l c u t t i n g . J a c k s o n ( ’3 1 ), by
a method o f d i s s o c i a t i o n i n w hich th e f o l l i c l e s w ere f r e e d
from th e c o n n e c tiv e t i s s u e , f i n d s t h r e e g e n e r a l form s in th e
human g la n d ; n am ely , a n g u l a r , ro u n d , and o v a l . He found
f o u r s i z e g ro u p s , th e a n g u la r f o l l i c l e s t e n d i n g to be l a r g e
and th e roun d ones s m a ll. The f o l l i c l e s v a ry i n s i z e and
shape a c c o rd in g to a g e . R ie n h o f f ( ’2 9 ) , by a method o f
m a c e r a tio n and m i c r o d i s s e c t i o n , was a b le to stu d y t h e i n d i
v i d u a l f o l l i c l e s o f th e human. T h e ir sh a p e , i n g e n e r a l ,
was s p h e r o i d a l ; h o w e v e r, no two w ere a l i k e , and t h e r e was
g r e a t v a r i a t i o n in s i z e a s w e l l a s form . He made r e c o n
s t r u c t i o n s and from them c o n c lu d e d t h a t t h e r e v/as no e v i
7
dence o f t h e p re s e n c e o f u n d i f f e r e n t i a t e d e p it h e l i u m
hetv/een f o l l i c l e s , "but t h a t f o l l i c l e s r e s u l t e d from t h e "bud
d in g o f p r e - e x i s t i n g f o l l i c l e s , a l l o f them "being c o m p le te ly
d i f f e r e n t i a t e d in t h e a d u l t .
A number o f i n t e r e s t i n g c o n t r i b u t i o n s h ave b e en made
c o n c e rn in g th e d i f f e r e n t i a t i o n o f t y p e s o f c e l l s v/hich a re
b e l i e v e d to be a s s o c i a t e d w ith th e f u n c t i o n o f s e c r e t i o n and,
b e c a u s e o f t h e i r l o c a t i o n in b o th t h e w a ll o f f o l l i c l e s and
i n i n t e r f o i l i c u l a r c e l l g ro u p , a r e th o u g h t by some to i n
f l u e n c e th e f o r m a tio n o f f o l l i c l e s . B e n sle y ( ’1 4 ) , in h i s
work on th e opossum, d e s c r i b e s a ty p e o f o v o id c e l l s , co n
t a i n i n g a h i g h ly g r a n u l a r c y to p la s m and l y i n g c lo s e to th e
w a ll o f t h e f o l l i c l e . He c o n c lu d e s t h a t t h e s e c e l l s a r e a
s p e c i a l ty p e o f e p it h e l i u m w hich i s a s s o c i a t e d w i t h th e s e
c r e t o r y p r o c e s s o f th e g la n d .
S e e c o ff ( ’27) fo u n d , in a stu d y o f th e t h y r o i d g la n d
o f th e human and in a number o f o t h e r mammals, num erous
h e a v i l y s t a i n e d c e l l s s c a t t e r e d th r o u g h o u t, f r e q u e n t l y in
th e i n t e r f o i l i c u l a r sp a c e s and p a r i e t a l in p o s i t i o n to th e
f o l l i c l e s a s d e s c r i b e d by B e n sle y c o n c e rn in g th e "o v o id
c e l l s . " S e e c o f f c a l l s t h e s e " m i t o c h o n d r i a - r i c h c e l l s . " He
c la im s t h a t th e s i g n i f i c a n c e o f t h e s e c e l l s i s unknown b u t
t h a t th e y a r e i n f lu e n c e d by age o r by th e f o r m a tio n o f a d e
nomas o r b o t h .
N onidez ( ’32a) found a second e p i t h e l i a l component
8
i n th e t h y r o i d o f t h e dog and, i n a l a t e r i n v e s t i g a t i o n
(* 3 2 h ), in t h a t o f th e c a t . The f o l l i c u l a r c e l l s e n l a r g e ,
and a r g y r o p h i l e g r a n u l e s form i n th e c y to p la s m . These sp e
c i a l c e l l s , w hich he c a l l s " p a r a f o l l i c u l a r c e l l s , " th e n s e
p a r a t e from th e w a l l s o f th e f o l l i c l e s and form l o o s e c l u s
t e r s in th e i n t e r f o i l i c u l a r s p a c e s . S in ce s e g r e g a t i o n s o f
t h e s e c e l l s o c c u r a t a tim e when c o l l o i d b e g in s to be s t o r e d
i n th e f o l l i c l e s , he c o n c lu d e s t h a t t h e r e a r e two ty p e s o f
c e l l s in th e w a l l s o f t h e f o l l i c l e s , one s e c r e t i n g i n t o th e
f o l l i c l e lumen and th e o t h e r i n t o th e i n t e r f o i l i c u l a r sp a c e .
He does n o t s u p p o r t W ilson ( ’ 2 7 - ’ 28) in th e c o n c l u s i o n t h a t
th e i n t e r f o i l i c u l a r c e l l m asses a r e t i p s o f sm a ll f o l l i c l e s .
Raymond ( ’ 32) fou nd th e same com ponents in th e r a b b i t .
Z ech el ( ’ 3 1 , ’32, and ’ 3 3 ) , in h i s stu d y o f th e dog
and l a t e r o f t h e human, c la im s th e e x i s t e n c e o f two g ro u p s
o f i n t e r f o i l i c u l a r c e l l s , t h o s e em bryonic i n n a t u r e a w a i t
in g dev elo pm ent i n t o f o l l i c l e s and th o s e a r i s i n g from th e
b r e a k in g up o f f o l l i c l e s . Among th e l a t t e r a r e l a r g e c e l l s ,
" m a c r o th y r o c y te s " , w hich he b e l i e v e s a re c o n c e rn e d w ith
(1 ) f o r m a tio n o f new f o l l i c l e s , (2) p r o d u c t i o n o f c o l l o i d ,
and (3) p o s s i b l y i n c e p t i o n o f f o l l i c u l a r d e s t r u c t i o n . Con
c e r n i n g f o l l i c l e s he s t a t e s : "The f o l l i c l e i s n o t a perm a
n e n t s t r u c t u r e b u t m erely a phase in s t r u c t u r a l metamorpho
s i s w hich a l t e r n a t e s b etw een two e x tre m e s , th e f o l l i c l e on
one end and t h e i n t e r s t i t i a l c e l l g ro u p on t h e o t h e r . "
9
Cowdry ( ’ 32) b e l i e v e s t h e s e t y p e s o f c e l l s d e s c r i b e d
by v a r i o u s i n v e s t i g a t o r s a r e d i f f e r e n t s t a g e s i n t h e s e c r e
t o r y c y c le o f t h e " c h i e f " o r common t h y r o i d c e l l .
Godwin ( ’3 7 ) , in a s tu d y o f th e dog t h y r o i d , l a y s
s p e c i a l em phasis on t h e r e l a t i o n o f th e u l ti m o b r a n c h i a l body
to th e i n t e r f o i l i c u l a r c e l l s . He c o n c lu d e s t h a t t h e u l ti m o -
b r a n c h i a l b o d ie s a r e i n c o r p o r a t e d w i t h i n th e body o f th e
t h y r o i d g la n d b u t fo llo v / a lo n g a s e p a r a t e l i n e o f d e v e lo p
ment from t h a t o f th e t h y r o i d p r o p e r , e v e n t u a l l y g i v i n g r i s e
to a s p e c i a l ty p e o f c e l l s . These a r e l a r g e r th a n t h e com
mon t h y r o i d c e l l and a r e a s s o c i a t e d v/ith t h e s e c r e t o r y
f u n c t i o n .
Only two p u b l i c a t i o n s have b een foun d d e a l i n g w ith
th e t h y r o i d g la n d o f th e h o r s e . One by R e i s i n g e r ( ’28)
g i v e s a b r i e f g e n e r a l a c c o u n t o f th e g r o s s and m ic ro s c o p ic
s t r u c t u r e o f t h e a d u l t g l a n d , and th e o t h e r , a d i s s e r t a t i o n
by Arx ( ’ 2 8 ) , g i v e s a th o ro u g h , d e t a i l e d r e p o r t from th e
one day o l d c o l t to t h e a d u l t in o ld a g e . No r e p o r t h a s
b e e n fou nd in th e l i t e r a t u r e re v ie w e d c o n c e rn in g t h e d e v e
lo p m e n t o f th e g la n d d u r i n g p r e n a t a l l i f e .
I I I . m im iA L AND M ETHODS
T h is i n v e s t i g a t i o n o f th e t h y r o i d g la n d i s b a s e d
upon a c o l l e c t i o n o f h o r s e embryos s e c u r e d from a l o c a l
s o u r c e . The embryos v a r i e d in s i z e from 5 mm. to 230 mm.
crown-rump m easurem ent a s shovm in th e f o l lo w in g t a b l e ;
T h ic k n e ss o f Sec
C. R. L en g th Type o f S e c tio n
5 mm............................... c r o s s . . .
6 mm. .......................l o n g i t u d i n a l
9 mm........................ ..... c r o s s . . .
13 mm...............................c r o s s . . .
1 4 .5 mm..........................c r o s s . . .
16 mm...............................c r o s s . . .
18 mm............................ l o n g i t u d i n a l
19 mm..............................s a g i t t a l
21 mm...............................c r o s s . . .
30 mm...............................c r o s s . . .
35 mm............................. c r o s s . . .
55 mm..............................s a g i t t a l
60 mm............................... c r o s s . . .
87 mm...............................c r o s s . . .
100 mm...............................c r o s s . . .
108 mm...............................c r o s s . . .
t i o n i n M icro ns
10*
14*
14*
20 *
10*
6
6
6
6
6
20 *
20 *
6
6
6
6
N o te : S e r i a l s e c t i o n s lo a n e d from zo ology d e p a rtm e n t
o f t h e U n i v e r s i t y .
11
Thicîcness o f Sec-
C. R. L e n g th Type o f S e c ti o n t i o n in M icrons
117 mm. . . . . . . c r o s s ................................ 6
158 mm.................................c r o s s ................................................. 6
180 mm. . . . . . . c r o s s . . . . . . . . . 6
230 mm.................................c r o s s ................................................. 6
A d u l t .................................c r o s s ................................................. 6
The embryos w ere f i x e d i n B o u in ’ s s o l u t i o n , d e h y d ra
t e d s u c c e s s i v e l y i n 70^, 80?&, 9 0 ^ , 95^ and a b s o l u t e s o l u
t i o n s o f e t h y l a l c o h o l , c l e a r e d in t o l u o l , and i n f i l t r a t e d
w ith p a r a f f i n c o n t a i n i n g b a b e r r y wax. The c l e a r i n g was done
g r a d u a l l y by p u t t i n g t h e t i s s u e s s u c c e s s i v e l y in th e f o l lo w
in g l i q u i d s :
1 p a r t t o l u o l , 3 p a r t s a b s o l u t e a lc o h o l
2 p a r t s t o l u o l , 2 p a r t s a b s o l u t e a lc o h o l
3 p a r t s t o l u o l , 1 p a r t a b s o l u t e a lc o h o l
P u re t o l u o l u n t i l c le a x
The tim e in each l i q u i d v a r i e d a c c o rd in g to t h e s i z e o f th e
embryo, th e a p p e a ra n c e o f th e m a t e r i a l i n d i c a t i n g when c l e a r
in g was c o m p le te d .
The i n f i l t r a t i o n , a l s o , was done g r a d u a l l y by sh av
in g p a r a f f i n i n t o t h e t o l u o l from tim e to tim e and l e a v i n g
f o r s e v e r a l h o u r s f i r s t in room t e m p e r a t u r e , th e n in an oven
a t 210 c . , and l a t e r in one a t 550 0 . When th e s a t u r a t i o n
p o i n t o f t h e t o l u o l was r e a c h e d i n t h e te m p e r a tu r e o f
12
55® C. th e t i s s u e s w ere p u t i n t o p u re p a r a f f i n , w hich was
changed tw ic e . A f t e r t h i s th e y were embedded in p a r a f f i n to
w hich b a b e r r y wax was added in th e r a t i o o f one to t e n .
A ll embryos o v e r 87 mm. i n l e n g t h w ere d e c a l c i f i e d
in a 396 s o l u t i o n o f h y d r o c h l o r i c a c id in 80^ a l c o h o l . The
tim e r e q u i r e d v a r i e d from f i v e to t e n d a y s d e p e n d in g upon
th e amount o f c a lc iu m p r e s e n t . When th e t i s s u e s w ere r e
moved from th e a c i d a l c o h o l , th e y w ere p u t in 80^ a lc o h o l
f o r s e v e r a l d a y s , t h e a lc o h o l b e in g changed d a i l y .
A ll s e r i e s p r e p a r e d e s p e c i a l l y f o r t h i s stu d y w ere
s e c t i o n e d a t 6 m ic ro n s . O th e r s e r i e s l i s t e d w ere lo a n e d
from th e z o o lo g y d e p a rtm e n t o f th e U n i v e r s i t y . The s e c t i o n s
w ere mounted in dam ar. I r o n h e m a to x y lin , e o s i n , and J e n s e n ’ s
t r i p l e d i f f e r e n t i a l s t a i n w ere u se d f o r s t a i n i n g :
(A) Form ula:
1 . Orange G— — — ( lOOOcc. ) — — — — 700 mg.
2. P i c r i c A cid S a t . Aq. S o l.
3 . A cid F u c h s in — ( 5 0 0 c c . ) — 540 mg.
( o r 1 g . p e r 1)
(B) S o l u t i o n :
1 . P i c r i c A cid S a t. Aq. S o l . ------ 8 0 cc.
2. A cid Fuchs in S o l . — — — — — — — — — — — 30 c c .
3 . A b s o lu te E th y l A lc o h o l------------3 0 c c .
(C) D is p e n s in g :
To 2 0 0 C C . o f (B) add lOOcc. o f Orange G
A ll s o l u t i o n s b u t (A -2 ), 30^ A lc o h o l
In most s e r i e s th e odd num bered s l i d e s w ere s t a i n e d by one,
and t h e even num bered ones by th e o t h e r . T h is p roved advan
ta g e o u s in t h e i n t e r p r e t a t i o n o f th e t i s s u e s .
13
The c a m e r a - lu c i d a was u se d to s k e tc h s p e c i f i c d e t a i l s
in some o f th e s e c t i o n s . P h o to m ic ro g ra p h s w ere made o f t h e s e
d ra w in g s and o f v a r i o u s c r o s s - s e c t i o n s to i l l u s t r a t e t h e d e s
c r i p t i o n s .
A model was c o n s t r u c t e d a c c o rd in g to th e H a r r i s o n
( ’ 24) m ethod from th e c r o s s - s e c t i o n s o f th e t h y r o i d g la n d
i n th e 35 mm. em bryo. The g la n d a t t h i s s ta g e i s so com
p l e t e l y b ro k e n up i n t o sm all p l a t e s and c o rd s w hich a r e sup
p o r t e d o n ly by th e c o n n e c tiv e t i s s u e t h a t some w i r i n g was
n e c e s s a r y to p r e s e r v e t h e c o r r e c t r e l a t i o n s h i p s o f p a r t s .
The f o u n d a t i o n o f th e model was c o v ered w i t h wax, w hich was
th e n c o a te d w ith p a r a f f i n so t h a t i t would p h o to g ra p h w e l l .
IV. OBSERVATIONS AND FINDHIGS
The E a r ly Developm ent o f th e T h y ro id Gland o f th e
H o r s e . The a n la g e o f th e t h y r o i d g la n d in t h e h o r s e , a s in
o t h e r mammals upon w hich o b s e r v a t i o n s by o t h e r s have b een
made, i s a m edian, v e n t r a l é v a g i n a t i o n o f t h e entoderm o f
th e f l o o r o f th e p h a ry n x a t th e l e v e l o f th e f i r s t and s e c
ond p h a ry n g e a l p o u c h e s. The p o s i t i o n o f t h i s é v a g i n a t i o n
i s shown by th e o p e n in g ( f i g . 1) in th e c r o s s - s e c t i o n th ro u g h
t h i s r e g i o n in t h e 5 mm. embryo. Younger embryos th a n th e
5 mm. embryo were n o t a v a i l a b l e to th e w r i t e r , so i t i s im
p o s s i b l e to s t a t e from p e r s o n a l o b s e r v a t i o n s j u s t when th e
a n la g e f i r s t a p p e a r s . A c co rd in g to Maximow and Bloom ( ’34)
i t o c c u r s i n human embryos a s e a r l y as th e 1 .3 7 mm. s t a g e ,
and N o r r i s ( ’18) o b se rv e d i t in s e v e r a l humans a t th e 2 mm.
s t a g e . Inasm uch as t h e d e s c r i p t i o n o f th e d i f f e r e n t s t a g e s
o f developm ent in th e h o r s e from th e 5 mm. to t h e 9 mm. s i z e s
p a r a l l e l r a t h e r c l o s e l y th o s e g iv e n f o r t h e human embryos o f
th e same s i z e s , i t may be co n clu d ed t h a t th e e a r l i e s t d e v e
lo pm ent o f th e g la n d in th e h o r s e c o rr e s p o n d s c l o s e l y to
t h a t o f th e human.
H orse embryo ^ mm. j n 1 e n g t h . S e r i a l c r o s s - s e c t i o n s
c u t a t 10 m ic ro n s show an o p e n in g j u s t p o s t e r i o r to th e t u -
b ercu lu m irapar and s l i g h t l y a n t e r i o r to t h e b a s e s o f th e
f i r s t b r a n c h i a l c l e f t s ( f i g . 1 ) . T h is m arks t h e r e g i o n
from w hich th e d i v e r t i c u l u m a r i s e s . The s i z e o f th e o p e n in g
F i g . 1 . A cam era l u c i d a s k e tc h o f a s e c t i o n o f th e
5 mm. embryo show ing t h e foram en w hich marks t h e p o s i t i o n
o f t h e a n la g e o f th e t h y r o i d g l a n d , x 85
ÀA-1 a o r t i c a r c h 1 o v .
FC, foram en
P I ,
HA, h y o id a rc h
PH,
MA, m a n d ib u la r a r c h RP,
MY, m yencephalon
T I.
o t i c v e s i c l e
p h a ry n g e a l pouch 1
p h a ry n x
R a th k e ’ s pouch
tu b e rc u lu m im par
M
AA.l
F ig . 1
15
i n d i c a t e s t h a t th e a n la g e i s a r a t h e r e x te n s i v e é v a g i n a t i o n
a s in th e c a s e o f th e human ( N o r r i s ’1 8 ) , and inasm uch a s th e
b ro a d o p e n in g d o es n o t e x te n d beyond tw e n ty m ic ro n s , i t i s ,
in t h i s embryo a t l e a s t , a v e ry s h a llo w d e p r e s s i o n . At a
d i s t a n c e o f t h i r t y m ic ro n s p o s t e r i o r w a r d a sm a ll d u c t i s
a p p a r e n t around w hich e p i t h e l i a l c e l l s a r e c l o s e l y packed
( f i g . 2 ) . F i f t y m ic ro n s p o s t e r i o r w a r d th e d u c t may be ob
s e r v e d , b u t t h e a r e a o f c e l l p r o l i f e r a t i o n i s more e x te n
s i v e , th e c e l l s p u s h in g o u t i n t o th e mesenchyme from th e
d u c t ( f i g . 3 ) . From t h e s e s e c t i o n s i t i s e v id e n t t h a t th e
d i v e r t ic u m i n t h i s p a r t i c u l a r embryo i s a h o llo w t u b e , in
th e w a ll o f w h ich , e s p e c i a l l y a t th e b a s e o f th e t u b e , c e l l
p r o l i f e r a t i o n o c c u r s .
The mesenchymal c e l l s o f th e s u r r o u n d in g t i s s u e a r e
d i s t i n g u i s h e d from t h e s e e p i t h e l i a l c e l l s by n u c l e i w hich
a r e more e lo n g a te d th a n th o s e o f th e e p i t h e l i a l c e l l s and
th e c h ro m a tin g r a n u l e s w i t h i n th e n u c l e i a r e s m a lle r and n o t
so d e e p ly s t a i n e d .
H orse embryo 6 mm. 1 e n g t h . In t h i s s e r i e s o f
s l i d e s t h e s e c t i o n s w ere c u t a t 14 m ic ro n s . The embryo was
c u rv e d in su ch a way t h a t th e r e g i o n w here th e t h y r o i d was
l o c a t e d was c u t l o n g i t u d i n a l l y b u t a t an a n g le o b liq u e to
th e p la n e r u n n in g from th e l e f t to r i g h t s i d e .
H ere th e c e l l s o f th e g la n d have a r r a n g e d th e m s e lv e s
F ig . S. A cam era l u c i d a s k e t c h show ing a t r a n s v e r s e
s e c t i o n o f t h y r e o g l o s s a l d u c t and e p i t h e l i a l c e l l s in i t s
w a ll 30 m ic ro n s p o s t e r i o r w a r d from f l o o r o f p h a ry n x , x 800
F ig . 3. Camera l u c i d a s k e tc h showing a t r a n s v e r s e
s e c t i o n th ro u g h b a s e o f t h y r e o g l o s s a l d u c t and e p i t h e l i a l
c e l l mass o f p r i m o r d i a l t h y r o i d g l a n d , 50 m ic ro n s from
f l o o r o f p h a ry n x , x 800
EP , e p i t h e l i a l c e l l s i n w a ll o f d u c t
EP C, e p i t h e l i a l c e l l mass
TH D, t h y r e o g l o s s a l d u c t
TH D
EPC
. o
F i g . 2
THD
: '-r . •
PC
F i g . 3
16
i n t o a d e f i n i t e p l a t e ( f i g . 4 ) , w hich i s d i s t i n c t l y s e t o f f
from t h e s n r r o n n d in g c e l l s and i s s e p a r a t e d from t h e ph ary n x
e x c e p t f o r a few im p e r f e c t s t r a n d s o f s c a t t e r e d c e l l s . H i s
t o l o g i c a l l y t h e c e l l s a p p e a r a s b e in g a l l o f one t y p e . The
n u c l e i a r e l a r g e b o d i e s , ro u n d o r o v a l i n sh a p e , c o n t a i n i n g
t h r e e o r f o u r d e e p ly s t a i n e d c h ro m a tin m a s se s. Ho c e l l
b o u n d a r i e s a r e a p p a r e n t . The n u c l e i o f t h e c e l l s i n th e
p e r i p h e r a l r e g i o n o f th e p l a t e a r e p r e s s e d c l o s e l y t o g e t h e r
and a r e a r r a n g e d w i t h t h e i r lo n g a x e s p e r p e n d i c u l a r to th e
s u r f a c e s o f t h e p l a t e ( f i g . 5 ) . The d e t a i l s o f s t r u c t u r e
a r e re m a rk a b ly s i m i l a r to t h o s e o b s e rv e d by H o r r i s (*18) i n
human embryos v a r y i n g from 4 .9 mm. to 7 mm.
H o rse embryo 9 mm. j n 1 e n g t h . E x a m in a tio n o f th e
s e c t i o n s o f t h i s embryo shows t h e t h y r o i d g la n d to be s t i l l
an i r r e g u l a r p l a t e w h ich h a s i n c r e a s e d in s i z e to more th a n
tw ic e t h a t o f t h e p l a t e o f t h e 6 mm. s t a g e , and w hich h a s
moved caudad to a p o s i t i o n n e a r t h e v e n t r a l a o r t a , ( f i g . 6 ) .
The a n t e r i o r b o u n d a ry o f t h e p l a t e h a s s e v e r a l p r o j e c t i o n s
e x te n d in g c e p h a la d , w hich may be e v id e n c e o f i t s r e c e n t s e
p a r a t i o n from t h e d u c t t h a t c o n n e c te d i t w i t h th e f l o o r o f
th e p h a ry n x . A p o r t i o n o f th e t h y r o g l o s s a l d u c t s t i l l r e
m ains a t t h i s s t a g e , e x te n d in g from t h e f l o o r o f th e p h a r
y n x . As y e t t h e g la n d shows no e v id e n c e o f becom ing b i -
l o b e d . The p l a t e i s a s o l i d mass o f c e l l s w i t h t y p i c a l
F i g . 4. Camera l u c i d a s k e t c h o f a l o n g i t u d i n a l
s e c t i o n th ro u g h th e t h y r o i d p l a t e o f a 6 mm. embryo show
in g i t s s e p a r a t i o n from t h e f l o o r o f th e p h a ry n x , and a
few e p i t h e l i a l s t r a n d s m arking t h e p o s i t i o n o f th e t h y r e o
g l o s s a l d u c t. X 120
F i g . 5. Camera l u c i d a s k e tc h o f e p i t h e l i a l p l a t e
o f t h y r o i d g la n d i n a 6 mm. embryo e n la r g e d to show th e
a rra n g e m e n t o f c e l l s w i t h i n t h e p r i m o r d i a l p l a t e , x 480
B TH B, b a s e o f t h y r e o g l o s s a l d u c t
EP P , e p i t h e l i a l p l a t e o f t h y r o i d
EP S , e p i t h e l i a l s t r a n d s
m
9
m yencephalon
H
9
n o to c h o r d
OV
9
o t i c v s s l c l e
PH
9
p h a ry p x
TH P , t h y r o i d p l a t e
IT u l t i m o b r a n c h i a l body
a fA k :
:;a:
y
F i g . 4
F ig . 5
E P S
ÏS »
TH D
«
THrÆ
i
^ W S
F ig . 6, A p h o to m ic ro g ra p h shov/ing a t r a n s v e r s e
s e c t i o n th ro u g h th e t h y r o i d p l a t e o f a 9 mm. em hryo.
X 80
H , h e a r t
PH , p h a ry n x
TH H, t h y r e o g l o s s a l d n c t
Th P , t h y r o i d p l a t e
F ig . 6
17
o v o id a l n u c l e i such a s d e s c r i b e d f o r th e 6 mm. em bryo.
T here a r e no e v id e n c e s o f any i n t r a g i a n d u l a r c a v i t i e s in
th e specim en s t u d i e d . I f t h i s i s t h e g e n e r a l c o n d i t i o n o f
a l l 9 mm. h o r s e em bryos, i t i s a d e p a r t u r e from t h a t o f th e
human. In th e l a t t e r , a c c o r d i n g to h o r r i s ( ' 1 8 ) , a number
o f c o m p le te ly c l o s e d c a v i t i e s a p p e a r w i t h i n t h i s g la n d mass
o f embryos o f a b o u t 7 mm.
Horse embryo 15 mm. i n l e n g t h . The t h y r o i d g la n d i n
t h i s s t a g e l i e s i n c l o s e p r o x im ity to th e v e n t r a l a o r t a and
i s s i t u a t e d v e n t r a l to th e p h a ry n x , j u s t a n t e r i o r to th e
g l o t t i s .
The b i l o b e d n a t u r e o f th e g la n d i s w e l l e s t a b l i s h e d
a t t h i s tim e . The l o b e s a r e d i s t i n c t , a b o u t eq.ual i n s i z e ,
and each o f them e x te n d in g th r o u g h a d i s t a n c e o f a b o u t 200
m ic r o n s . They seem to be somewhat s p h e r i c a l i n o u t l i n e .
The isth m u s i s s h o r t and a p p a r e n t l y q u i t e b r o a d . The embryo
was t u r n e d i n su ch a way t h a t t h e s e c t i o n s w ere c u t q u i t e
o b l i q u e l y , and in some o f them th e d i s t a l lo b e and a p o r
t i o n o f t h e is th m u s w ere p a r t l y c o n c e a le d b e h in d th e p r o
x im a l l o b e . B ecause o f t h i s , i t i s im p o s s ib le to sp eak
w i t h a b s o l u t e c e r t a i n t y a s to th e e x a c t shape o f l o b e s and
is th m u s .
The a rra n g e m e n t o f t h e n u c l e i o f t h e c e l l s i n each
l o b e i s t y p i c a l to t h a t o f th e i n i t i a l p l a t e a s d e s c r i b e d
18
u n d e r t h e 6 mm. embryo. A c l o s e e x a m in a tio n o f a l l s e c t i o n s
u n d e r a h i g h m a g n i f i c a t i o n r e v e a l s , a l t o g e t h e r in b o t h l o b e s ,
n o t more th a n h a l f a dozen m in u te c a v i t i e s w hich a re
c o m p le te ly e n c lo s e d in th e c e l l m ass. The s e c t i o n s a r e c u t
a t SO m ic ro n s , how ever, so t h a t i t i s p o s s i b l e t h a t n o t a l l
o f them a r e e v i d e n t . In any c a s e th e y a r e few i n number
and e x tre m e ly s m a ll. They a p p e a r s t r i k i n g l y l i k e t h o s e d e s
c r i b e d by H o r r i s ( '1 8 ) i n t h e human embryo o f 7 mm. He d e s
c r i b e s them a s " t i n y c l e f t s , a p p e a r in g v e ry much a s th o u g h
t h e c e l l s a ro u n d them had b u t p u l l e d a l i t t l e a p a r t . "
I n t h i s p a r t i c u l a r em bryo, a t l e a s t , th e c o n c l u s i o n
t h a t t h i s s t a g e o f d ev elo p m e n t m arks th e b e g in n i n g o f t h e
b r e a k i n g up o f th e s o l i d e p i t h e l i a l p l a t e i n t o a s e r i e s o f
f e n e s t r a t e d p l a t e s i s j u s t i f i e d .
The u p p e r end o f t h e h o llo w t u b e , by means o f w hich
t h e t h y r o i d c e l l mass was a t f i r s t susp en d ed from t h e f l o o r
o f t h e p h a ry n x , s t i l l p e r s i s t s . I t i s t h i s rem n an t o f th e
tu b e t h a t i s known a s th e "C anal o f H i s . " (M arine ' 3 S ) .
H orse embryo 1 4 .5 mm. i n 1 e n g t h . H ere th e t h y r o i d
g la n d i s fou nd l y i n g c l o s e to th e t r a c h e a j u s t v e n t r a l to
t h e p o s t e r i o r end o f t h e p h a ry n x . I t t e r m i n a t e s im m ed iate
l y a n t e r i o r to w here th e p h a ry n x n a rro w s down to th e g u l l e t .
The l o b e s e x te n d d o r s o - l a t e r a l l y a lo n g t h e s i d e s o f th e
l a r y n x i n th e r e g i o n o f th e g l o t t i s , and t h e isth m u s c r o s s e s
19
th e v e n t r a l s u r f a c e o f th e l a r y n x . I t i s im p o s s ib le to s tu d y
th e isth m u s to any e x t e n t i n t h i s s e r i e s b e c a u se o f damage
to th e t i s s u e s in t h a t a r e a . The l o b e s , how ever, a r e in
good c o n d i t i o n and show t h a t th e y have i n c r e a s e d in s i z e to
320 m ic ro n s i n l e n g t h . A number o f i n t r a g l a n d u l a r c a v i t i e s
a p p e a r in t h e t h i c k e r p o r t i o n s o f t h e l o b e s . These c a v i t i e s
v a r y from mere s l i t - l i k e o p e n in g s , such a s found i n t h e 13
mm. s t a g e , to f a i r l y l a r g e o n e s , t h e l a t t e r b e in g form ed by
th e m erg in g o f s m a ll e r o n e s . T h is m erg in g i s c l e a r l y e v i
d e n t i n many o f t h e s e c t i o n s . In a few i n s t a n c e s th e c a v
i t i e s open to th e e x t e r i o r , and v a s c u l a r mesenchymal t i s s u e
i s o b s e rv e d m i g r a t i n g in w a rd . T here a r e many b lo o d v e s s e l s
a p p e a r in g j u s t e x t e r i o r to t h e p e r i p h e r y o f th e l o b e s .
L o c a te d d o r s a l l y to each lo b e and s l i g h t l y n e a r e r
th e m edian l i n e o f th e b o d y , i s a compact mass o f e p i t h e l i a l
c e l l s , s e t o f f from t h e c e l l s o f th e s u r r o u n d in g t i s s u e s by
a d i s t i n c t b o u n d a ry w hich a p p e a r s in c r o s s - s e c t i o n s to g iv e
t h e body a s p h e r i c a l o r o v a l s h a p e . A c c o rd in g to N o r r i s
( ' 1 6 ) , T o rn eaux and V erdun (1 8 9 7 ), and K in g s le y ( '1 4 ) and
o t h e r s , t h i s i s t h e l a t e r a l t h y r o i d a n l a g e , c a l l e d r e c e n t l y
th e " u l t i m o b r a n c h i a l b o d y ." These b o d i e s a r e n o t in c lu d e d
i n t h i s i n v e s t i g a t i o n .
H orse embryo 16 mm. in 1 e n g t h . An e x c e l l e n t s e r i e s
o f s l i d e s o f a 16 mm. embryo s e c t i o n e d a t 6 m ic ro n s makes
20
i t p o s s i b l e to o b se rv e d e t a i l s o f s t r u c t u r e w hich c o u ld n o t
be d e t e c t e d in th e 1 4 .5 mm. em bryo.
H e re , a s i n t h e s t a g e r e p r e s e n t e d by th e 1 4 .5 mm, em
b r y o , th e l o b e s a r e d e f i n i t e l y l o c a t e d one on e i t h e r s i d e o f
th e l a r y n x e x te n d in g from t h e g l o t t i s p o s t e r i o r w a r d v /ith
t h e i r lo n g a x e s r u n n in g p a r a l l e l to t h e t u b e . They a r e c o n
n e c t e d w ith one a n o th e r by an isth m u s a s in th e 1 4 .5 mm. em
b r y o , b u t now, th e g la n d h a s m ig r a te d f a r enough cau dad so
t h a t t h e isth m u s i s v e n t r a l to t h e f i r s t t r a c h e a l r i n g . In
t h i s c a s e , hov/ever, th e isth m u s h a s l e n g t h e n e d , and th e
t h i c k e r p o r t i o n o f t h e g la n d d o e s n o t l i e so c l o s e to t h e
v e n t r a l s u r f a c e o f th e t r a c h e a . The g la n d shows a com para
t i v e l y r a p i d i n c r e a s e in g ro w th , as i n d i c a t e d by th e f a c t
t h a t t h e c o m p lete s e r i e s o f c r o s s - s e c t i o n s , from th e extrem e
a n t e r i o r l i m i t s o f th e l o b e s to t h e p o s t e r i o r b o u n d a ry o f
th e is th m u s , e x te n d s th ro u g h a d i s t a n c e o f a b o u t 625 mi
c r o n s . One o f th e l o b e s m ea su re s a b o u t 462 m ic r o n s , an i n
c r e a s e o f 162 m ic ro n s o v e r t h e 1 4 .5 mm. s i z e , w hich i n d i
c a t e s t h e o n s e t o f a p e r i o d o f p ro n o u n ced c e l l p r o l i f e r a t i o n .
Toward t h e isth m u s t h e l o b e becom es s l e n d e r and e l o n g a t e d
so t h a t i t i s d i f f i c u l t to say j u s t v/here i t t e r m i n a t e s and
t h e is th m u s b e g i n s .
A ll o f t h e s e c t i o n s th r o u g h th e t h i c k e r p o r t i o n s o f
t h e l o b e s , marked by a r e g i o n a b o u t e q u a l ly d i s t a n t from th e
e x t r e m i t i e s o f each l o b e , show an i n c r e a s i n g number o f th e
F i g . 7 . A p h o to m ic ro g ra p h o f a c r o s s - s e c t i o n
th r o u g h t h e t h y r o i d g la n d o f a 16 mm. emhryo showing
i n t r a g l a n d u l a r c a v i t i e s , e n l a r g i n g w i t h i n t h e g l a n d ,
and one o p e n in g t o t h e e x t e r i o r a d m i t t i n g t h e i n v a s i o n
o f mesenchyme, x 280
C AR, c a r o t i d a r t e r y
E CA, c a v i t y o p e n in g to e x t e r i o r
S CA, sm a ll c a v i t y
L CA, l a r g e c a v i t y
5/
F ig . 7
21
i n t r a g l a n d u l a r c a v i t i e s , a l l w i t h d e f i n i t e , c l e a r - c u t m ar
g i n s ( f i g , 7 ) , T here i s a w ide v a r i a t i o n in s i z e and sh ape
i n t h e s e c a v i t i e s , and no d e f i n i t e p l a n o f a rra n g e m e n t i s
e v i d e n t . They a r e s c a t t e r e d p ro m is c u o u s ly th r o u g h o u t what
seems to be th e o l d e r p o r t i o n o f t h e g l a n d . The c a v i t i e s
seem to b e empty s p a c e s ; i f t h e r e i s a f l u i d , i t d o e s n o t
t a k e any o f t h e s t a i n s u s e d . T here i s no s p e c i a l p o s i t i o n
o f t h e c e l l s t h a t b o r d e r th e c a v i t y , a s i n d i c a t e d by th e
d i f f e r e n t a n g le s a t w hich t h e n u c l e i a r e t u r n e d , and by th e
f a c t t h a t th e n u c l e i may be a t some d i s t a n c e from t h e o p en
in g . At t h e two a n t e r i o r , d o r s a l e x t r e m i t i e s o f t h e l o b e s
th e s e c t i o n s show th e same c e l l a rra n g e m e n t a s t h a t o f th e
i n i t i a l p l a t e . H ere t h e g la n d i s o n ly a few c e l l s i n t h i c k
n e s s . I t i s p o s s i b l e t h a t t h e s e n a rr o w e r end r e g i o n s r e p r e
s e n t t h e new er p o r t i o n s o f t h e l o b e s . L a rg e c a v i t i e s have
form ed by t h e c o n flu e n c e o f s m a ll e r o n e s , such a s se en in
t h e two p r e v i o u s s t a g e s , and a r e more num erous th r o u g h o u t t h e
e n t i r e g la n d th a n a t any p l a c e i n t h e g la n d o f t h e 1 4 .5 mm.
s t a g e . A few o f t h e s e l a r g e r c a v i t i e s have opened t o th e
e x t e r i o r o f t h e g la n d ; h o w ev er, t h e l a r g e m a j o r i t y a r e s t i l l
c o m p le te ly i n c l o s e d . H ere a s i n th e p r e c e d i n g embryo th e
v a s c u l a r mesenchyme i s m i g r a t i n g i n t o th e i n t e r i o r , and up
on c l o s e o b s e r v a t i o n th e mesenchymal c e l l s and o c c a s i o n a l
b lo o d c o r p u s c l e s may b e seen s c a t t e r e d among t h e e p i t h e l i a l
22
c e l l s o f th e g l a n d . T h is b r e a k i n g up o f t h e t h y r o i d g la n d
in t h e e a r l y h o r s e embryos i n t o p l a t e s and c o r d s by i n t r a
g l a n d u l a r c a v i t i e s s u p p o r t s th e f i n d i n g s o f N o r r i s ( '1 8 ) i n
human em bryos. A c c o rd in g to Godwin ( ' 3 7 ) , no such c a v i t i e s
o c c u r in th e e a r l y dog em bryos.
Horse embryos 18 mm. and 19 mm. in 1 e n g t h . A s e r i e s
o f c r o s s - s e c t i o n s o f t h e t h y r o i d o f two 18 mm. embryos have
b e en a v a i l a b l e f o r e x a m in a tio n . The g la n d shows an i n c r e a s e
i n t o t a l l e n g t h o f 55 m ic ro n s o v e r th e 16 mm. em bryo. I t s
l o b e s l i e l a t e r a l to t h e c a r t i l a g e s o f th e l a r y n x , a p o s i
t i o n w hich i s a n t e r i o r to i t s f i n a l p o s i t i o n and o n ly s l i g h t
l y more caudad th a n t h a t i n t h e 16 mm.
There h a s b e e n a m arked advance o v e r t h e 16 mm. s ta g e
i n t h e p r o g r e s s i v e b r e a k i n g up o f th e s o l i d p l a t e - l i k e mass
i n t o s m a ll e r e p i t h e l i a l p l a t e s , a, few o f w hich a p p e a r a s
n a rro w b a n d s ( f i g . 8 ) . Each p l a t e i s more o r l e s s f e n e s t r a
t e d o r shows l o n g , n a rro w , c r a c k - l i k e o p e n in g s w hich r u n in
v a r i o u s d i r e c t i o n s a c r o s s th e sm a ll p l a t e s . The p l a t e s a r e
s e p a r a t e d e n t i r e l y o r i n p a r t from t h e n e i g h b o r i n g o n e s by
s e p t a w hich a p p e a r to be mere s y n c y t i a o f mesenchymal c e l l s
i n w hich may b e o b s e rv e d many b lo o d c o r p u s c l e s . I t i s e v i
d e n t t h a t t h e s e c h a n g e s have come a b o u t by t h e g ro w th o f th e
i n t r a g l a n d u l a r c a v i t i e s w h ic h , i n a s h o r t p e r i o d o f d e v e lo p
m ent, have opened to t h e e x t e r i o r and have b e e n in v a d e d by
F i g . 8. A p h o to m ic ro g ra p h o f an 18 mm. embryo
show ing t h e p r o g r e s s i v e b r e a k i n g up o f t h e t h y r o i d p l a t e
by th e f o r m a t io n o f c a v i t i e s and i n v a s io n o f mesenchyme.
X 280
CA , c a v i t y
C AR, c a r o t i d a r t e r y
I ME, in v a d in g mesenchyme
P ig . 8
23
t h e v a s c u l a r mesenchyme w h ich s u r r o u n d s t h e g l a n d .
The r e g i o n s to w ard th e e x t r e m i t i e s o f t h e l o b e s s t i l l
show t h e a rra n g e m e n t o f t h e e a r l y g l a n d , w h ile s e c t i o n s
t a k e n to w ard t h e c e n t e r o f t h e g la n d d u p l i c a t e t h e e a r l y
p e r i o d o f f e n e s t r a t i o n , and so on u n t i l a l l s t a g e s o f d e v e
lo p m e n t a r e found i n th e one g l a n d . T h is s u p p o r t s t h e id e a
t h a t g ro w th i n s i z e must t a k e p la c e in th e e x t r e m i t i e s o f
t h e l o b e s , and t h a t t h e r e i s p r o g r e s s i v e d i f f e r e n t i a t i o n de
p e n d in g , i n p a r t a t l e a s t , upon th e c h ro n o lo g y o f i n i t i a l
f o r m a t i o n . Up to t h i s s t a g e t h e r e i s no e v id e n c e o f any
c a v i t i e s among t h e c e l l s o f th e is th m u s .
Two embryos o f t h e 19 mm. s t a g e w ere a v a i l a b l e . One
was c u t in s e r i a l s e c t i o n s l o n g i t u d i n a l l y , and t h e o t h e r in
s e r i a l s e c t i o n s s a g i t t a l l y . They show a c o n ti n u e d b r e a k i n g
up o f t h e c e l l mass and a te n d e n c y to form n a rro w p l a t e s or
c o rd s o f t h e e p i t h e l i a l c e l l s . In t h e s e s e c t i o n s t h e g e n
e r a l o u t l i n e o f th e l o b e s a p p e a r s to b e g o u r d - s h a p e d , t a p e r
in g tov/ard th e is th m u s . The e l o n g a t i o n o f t h e g la n d g i v e s
e v id e n c e o f a r a p i d l o n g i t u d i n a l gro w th in t h e s e e a r l y
t h y r o i d s .
H orse embryo 21 mm. i n l e n g t h . I n t h i s embryo th e
l o b e s have i n c r e a s e d i n l e n g t h to 576 m ic ro n s , a b o u t 61 mi
c r o n s more th a n i n t h e 18 mm. The t o t a l 1 e n g th i n c l u d i n g
t h e isth m u s i s 618 m ic r o n s . The isth m u s i s a p p a r e n t l y b e -
24
coming r e l a t i v e l y s h o r t e r , w h ich i s e x p la in e d , no d o u b t, by
t h e p r o l i f e r a t i o n o f c e l l s on th e l a t e r a l l i m i t s o f each
l o b e . The p o s i t i o n o f th e g la n d w i t h r e s p e c t to th e l a r y n x
i s p r a c t i c a l l y t h e same a s t h a t o f t h e 18 mm. embryo.
I n th e s e r i e s o f embryos u se d in t h i s s tu d y th e 21
mm. s i z e m arks th e i n i t i a l s t a g e in t h e d evelo pm ent o f t h e
p rim a ry f o l l i c l e o f th e t h y r o i d g l a n d . The f o l l i c l e i s d e
f i n e d , by many who have s t u d i e d t h i s g l a n d , a s t h e u n i t o f
s t r u c t u r e , l i n e d w i t h a s i n g l e l a y e r o f e p i t h e l i a l c e l l s i n
c l o s i n g a lum en. In g e n e r a l , i t i s s p h e r i c a l o r s p h e r o i d a l
i n s h a p e , th o u g h v a r i a t i o n s a r e fo u n d . The s o - c a l l e d " p r i
mary" f o l l i c l e s a r e th o s e w hich a p p e a r f i r s t d u r i n g th e d e
v e lo p m en t o f th e g l a n d .
The p r o g r e s s i v e b r e a k i n g up o f t h e c o n tin u o u s e p i t h e
l i a l p l a t e s u n t i l a c o rd two c e l l s i n t h i c k n e s s i s d e r i v e d
seems to be t h e c o n d i t i o n to be a t t a i n e d i n p r e p a r a t i o n f o r
th e f o r m a tio n o f t h e f o l l i c l e . In t h i s embryo o n ly a few
s e c t i o n s th r o u g h t h e r e g i o n midway b e tw e e n t h e e x t r e m i t i e s
o f th e l o b e s show th e c o m p le te d f o r m a t io n o f t h e s e t w o - c e l l e d
c o r d s . Here and t h e r e a r e found e a r l y e v id e n c e s o f th e f o r
m a tio n o f f o l l i c l e s . The i n t e r e s t i n g f e a t u r e in t h i s r e g a r d
i s t h a t , in a c c o rd w ith th e e x p l a n a t i o n o f N o r r i s ('16) on
t h e d ev elo p m e n t o f t h e p rim a ry f o l l i c l e from th e t w o - c e l l e d
p l a t e , t h e b e g in n i n g o f a f o l l i c l e c a n be d e t e c t e d o n ly by
an a p p a r e n t d i s t u r b a n c e i n t h e a rra n g e m e n t o f th e c e l l s
25
w i t h i n th e p l a t e . T y p i c a l l y t h e c e l l s a r e a r r a n g e d i n such
a way t h a t t h e lo n g a x e s o f t h e i r n u c l e i a r e a t r i g h t a n g le s
to t h e s u r f a c e o f t h e p l a t e , b u t in an a r e a d e s t i n e d to form
a f o l l i c l e , j u s t a s i n th e human g l a n d s , a few o f t h e c e l l s
on e i t h e r s i d e o f t h e band and l y i n g n e x t to eac h o t h e r ,
move inw ard away from th e s u r f a c e and g r a d u a l l y t u r n a t an
a n g le t o i t , b r i n g i n g t h e in n e rm o st p o l e s o f t h e c e l l s i n to
c l o s e p r o x im ity ( f i g . 9). In c r o s s - s e c t i o n a s p h e r i c a l d e
s i g n i s form ed by t h i s g r o u p in g . The n u c l e i o f th e c e l l s
p u sh o utw ard tov/ard t h e p e r i p h e r y o f th e f i g u r e l e a v i n g a
c o m p a r a tiv e ly w id e , l i g h t l y s t a i n e d r e g i o n o f t h e c y to p la s m
i n t h e in n e r end o f each c e l l . Where t h e c e l l s move away
from t h e s u r f a c e o f th e p l a t e a sh a llo w i n d e n t a t i o n o c c u r s .
The b o u n d a r i e s o f many c e l l s a r e q u i t e d i s t i n c t , a f a c t
w hich i s made a p p a r e n t by t h e p e r f e c t c o n d i t i o n and e x c e l
l e n t s t a i n i n g o f t h e s e c t i o n s . In one sm a ll c i r c u l a r c l u s
t e r o f c e l l s , a t l e a s t h a l f o f them show m i t o t i c f i g u r e s in
t h e i r n u c l e i , g i v i n g e v id e n c e o f p r o l i f e r a t i o n . Some o f th e
g ro u p s show a v e ry p a l e c i r c u l a r a r e a i n t h e c e n t e r , w hich
u n d o u b te d ly m arks t h e f i r s t i n d i c a t i o n o f t h e lum en. Only
a v e ry l i m i t e d number o f f o l l i c l e s a r e fou nd i n t h i s s ta g e
o f d e v e lo p m e n t. By f a r th e g r e a t e r p o r t i o n o f th e l o b e s i s
s t i l l a com plex o f p l a t e s , b o t h b ro a d and n a rro w , w hich have
n o t y e t r e a c h e d t h e s t a g e o f t h e c o rd s two c e l l s in t h i c k
n e s s .
F i g . 9 . A c a m e r a - lu c i d a s k e tc h o f a p o r t i o n o f a
c r o s s s e c t i o n o f t h e t h y r o i d g la n d o f t h e 21 mm. embryo
showing th e a p p e a ra n c e o f two liim ina, and c e l l s moving away
from th e p e r i p h e r y o f th e t w o - c e l l e d c o rd and t u r n i n g a t an
a n g le to th e s u r f a c e i n t h e p r o c e s s o f fo rm in g p rim a ry
f o l l i c l e s .
B GO
EP
ID
1Ü
M CE
SE
b lo o d c o r p u s c l e
e p i t h e l i a l t i s s u e
i n d e n t a t i o n
lum en
c e l l s moving away from s u r f a c e
septum
CE
I / ' I '. ' :
........................................
F ig . 9
26
The c o n n e c ti v e t i s s u e c a p s u le h a s become a l o o s e n e t
work o f f i n e f i b e r s in w h ich lo n g n a rro w n u c l e i a r e l o c a t e d
p a r a l l e l i n g th e d i r e c t i o n o f t h e f i b e r s . The n u c l e i con
t a i n c h r o m a tin , b u t i t i s n o t a s d e e p ly s t a i n e d o r a s abun
d a n t a s in t h e p a ren ch y m al c e l l s o f th e g l a n d . The s e p t a b e
tw een t h e l o b u l e s e x te n d in w ard from t h i s c a p s u l e , b u t t h e y
do n o t show a s f i b r o u s a n a t u r e a s t h a t o f t h e c a p s u l e .
L a rg e s p a c e s open b e tw ee n t h e g l a n d u l a r t i s s u e and t h e c a p
s u l e , no 'd o u b t, t h e f o r e - r u n n e r s o f th e v e n o u s and ly m p h a tic
s p a c e s t h a t w i l l e v e n t u a l l y s u rro u n d th e g l a n d . As p o i n t e d
o u t i n e a r l i e r s t a g e s , c o r p u s c l e s a r e found in t h e c o n n e c
t i v e t i s s u e s e p t a .
H o rse embryo 30 mm. i n l e n g t h . The 30 mm. embryo
d o e s n o t show an i n c r e a s e i n t o t a l l e n g t h o v e r t h a t o f th e
21 mm.; h ow ever, t h e l o b e s show t h a t g ro w th i n t h e l a t e r a l
l i m i t s i s c o n t i n u i n g , r e s u l t i n g in t h e i r becom ing t h i c k e r
and w id e r n e a r t h e i r j u n c t i o n w ith t h e is th m u s . In a l l e a r
l i e r embryos th e p o s t e r i o r end o f each lo b e h a s b e e n e l o n
g a te d and h a s t a p e r e d to th e w id th o f th e is th m u s . T h is
w ould seem to i n d i c a t e t h a t t h e p o r t i o n o f t h e l o b e s n e a r
t h e isth m u s i s a r e g i o n o f r a p i d i n c r e a s e in l e n g t h a s th e
g la n d e l o n g a t e s . The p o s i t i o n o f th e l o b e s i s s l i g h t l y more
caudad th a n i n th e 21 mm. embryo.
W ith in th e g l a n d , e x c e p t a t th e e x t r e m i t i e s , most o f
th e p l a t e s and b a n d s o f any w id th have become n a rro w c o rd s
two c e l l s i n t h i c k n e s s w hich h a v e , on t h e w h o le , smooth s u r
f a c e s . Due t o some f a u l t in t e c h n iq u e i t i s im p o s s ib le to
s tu d y d e t a i l s o f c e l l a rra n g e m e n t w i t h i n t h e c o r d s . How
e v e r , an o c c a s i o n a l f o l l i c l e w hich h a s a c q u i r e d i t s lumen
may be d e t e c t e d in t h e p e r i p h e r a l ends o f some o f th e c o r d s .
Though d e t a i l s c a n n o t be s t u d i e d h e r e , th e s e c t i o n s d e f i n i t e
l y c o n t r i b u t e e v id e n c e o f th e g r a d u a l , p r o g r e s s i v e ch an g in g
o f t h e p l a t e - l i k e l o b u l e s i n to t h e s o - c a l l e d t w o - c e l l e d
c o r d s w h ich b e g a n , i n t h e s e p r e p a r a t i o n s , in th e 21 mm. em
b r y o . Thus i t c o n fo rm s v^ith t h e g e n e r a l o b s e r v a t i o n s made
on th e y o u n g er and o l d e r embryo in t h i s i n v e s t i g a t i o n ex
c e p t i n g in m a t t e r o f i t s t o t a l l e n g t h .
H orse embryo 35 mm. i n 1 e n g t h . Among t h e specim ens
a v a i l a b l e f o r t h i s s tu d y t h e 35 mm. embryo shows th e g r e a t
e s t advance i n th e b r e a k i n g up o f t h e g la n d i n t o a mass o f
i r r e g u l a r , b ra n c h e d c o r d s . The 55 ram. s t a g e , w hich f o llo w s
t h i s o n e , h a s p a s s e d t h e c lim a x o f t h i s d e v elo p m en t and b e
g i n s to show e v id e n c e o f th e b r e a k i n g down o f t h e c o r d s .
The c u lm i n a t io n o f t h e p r o c e s s i s r e a c h e d somewhere b etw een
t h e two s t a g e s . However th e 35 mm. embryo i s s u f f i c i e n t l y
adv an ced to show so m e th in g o f t h e f i n a l outcom e o f t h e p r o
c e s s .
The i m p r e s s io n o b t a i n e d from t h e s e c t i o n , a s th e d e -
28
v e lo p m e n ta l c h an g e s w ere t r a c e d from th e 18 mm, embryo to
t h e 35 mm,, i s t h a t t h e o r i g i n a l g la n d mass i s broken, up i n
to l o b u l e s w hich a r e c o n v e r te d i n t o p l a t e - l i k e m asses and
l a t e r i n t o i r r e g u l a r , b r a n c h i n g c o r d s . The l a c k o f c o n t i
n u i t y b e tw een t h e s u c c e s s i v e s e c t i o n s th ro u g h t h e more a d
v a n c e d r e g i o n o f t h e g l a n d , in th e 35 mm, and in t h e 55 mm.
em bryos, c a u s e d a q u e s t i o n to a r i s e a s to w h e th e r o r n o t th e
u l t i m a t e s t r u c t u r e i s a f e n e s t r a t e d , e p i t h e l i a l p l a t e two
c e l l s i n t h i c k n e s s and l o n g i t u d i n a l l y a r r a n g e d , such a s N o r
r i s fo u n d in t h e human. A model o f one o f t h e l o b e s was
c o n s t r u c t e d to v i s u a l i z e t h e a c t u a l r e s u l t s ( f i g . 10 and 1 1 ).
T h is model d e m o n s tr a te s t h a t t h e more ad v an ced d i f f e r
e n t i a t i o n o f t h e g la n d i s i n t h e p o s t e r i o r t w o - t h i r d s o f th e
l o b e s . In t h e a n t e r i o r e x t r e m i t y p l a t e s a r e s t i l l p r e s e n t .
These p l a t e s a r e s h a llo w , b u t a p p a r e n t l y more t h a n two c e l l s
i n t h i c l o i e s s . Some o f t h e s e show e v id e n c e o f a c o n tin u e d
b r e a k i n g u p . C a v i t i e s a r e p r e s e n t h e r e and t h e r e , and u n d e r
t h e m ic ro s c o p e t h e s e a r e fo u n d to c o n t a i n q u a n t i t i e s o f b lo o d
c o r p u s c l e s . In t h e lo w e r t w o - t h i r d s o f th e g la n d t h e r e i s a
mesh o f c o r d s , two c e l l s i n t h i c k n e s s , many o f w hich e x h i b i t
b r a n c h i n g and a n a sto m o sin g b e tw e e n t h e c o r d s . S m a ll, f e n e s
t r a t e d p l a t e s may s t i l l be fo u n d among th e c o r d s . However,
t h e s e show t h a t th e y a r e s t i l l i n t h e p r o c e s s o f b e in g b r o
k en down. T here i s no e v id e n c e o f an a rra n g e m e n t o f e i t h e r
c o r d s o r p l a t e s i n a p la n e l o n g i t u d i n a l l y p la c e d w i t h r e s p e c t
F i g . 1 0 . A p h o to g ra p h o f a model show ing th e p o s
t e r i o r - m e d i a n v iew o f a lo b e o f t h e t h y r o i d g la n d in t h e
35 mm. embryo, x 120
F i g . 1 1 . A p h o to g ra p h o f a model show ing th e p o s
t e r i o r - l a t e r a l v iew o f th e t h y r o i d g la n d o f a 35 mm. em bryo.
X 120
CD
EP
EP P
I — I
IS
LO
SE
c o rd s e x te n d in g to p e r i p h e r y o f g l a n d
sm a ll e p i t h e l i a l mass
e p i t h e l i a l p l a t e i n a n t e r i o r e x t r e m i t y
c r o s s s e c t i o n shown i n F i g . 12
isth m u s
l o b u l e
septum
F ig . 10
F ig . 11
29
to t h e l o n g a x i s o f th e b o d y . In g e n e r a l th e p l a n o f a rran g e-
ment i s t r a n s v e r s e th o u g h c o rd s hav e b e e n fo u n d e x te n d in g in
d i r e c t i o n s ( f i g . 1 2 ) . On th e w h o le, t h e c o r d s a r e in d e
p e n d e n t o f each o t h e r , s u p p o r te d by c o n n e c ti v e t i s s u e o n l y .
T h is f a c t made i t n e c e s s a r y to do some w i r i n g to g i v e su p
p o r t to th e c o rd s and t o p r e s e r v e t h e i r s p a t i a l r e l a t i o n
s h i p s . O c c a s i o n a l l y a s o l i d o r h o llo w f o l l i c l e may b e fo und
c o m p le te ly d e ta c h e d and s u rro u n d e d by th e i n t e r s t i t i a l t i s
s u e . In t h e isth m u s sm a ll p l a t e s a r e s t i l l a p p a r e n t . T h is
f a c t s u p p o r t s th e e v id e n c e fo u n d i n e a r l i e r embryos t h a t th e
is th m u s i s more r e t a r d e d i n i t s d evelo p m en t t h a n th e p o s
t e r i o r e x t r e m i t y o f t h e l o b e s . A l l aro u n d t h e o u t e r b o un
d a r y o f t h e g l a n d a r e sm a ll m asses o f parenchym al t i s s u e ,
w h ich have become s e g r e g a t e d from th e m ain m ass. T h is w ould
i n d i c a t e t h a t t h e p e r i p h e r a l r e g i o n i s s l i g h t l y i n advance
o v e r t h e c e n t r a l r e g i o n in i t s d i f f e r e n t i a t i o n .
T h ere i s no e v id e n c e t h a t t h e p r im a r y f o l l i c l e s i n
t h e h o r s e embryo d e v e lo p from f e n e s t r a t e d , e p i t h e l i a l p l a t e s ,
l o n g i t u d i n a l l y a r r a n g e d , b u t r a t h e r from i r r e g u l a r b r a n c h e d
c o r d s two c e l l s i n t h i c k n e s s .
H orse embryo 55 mm. i n l e n g t h . No embryos b e tw e e n
t h e 35 mm. and 55 mm. s i z e s have b e e n a v a i l a b l e f o r o b s e r v a
t i o n , b u t th e 55 mm. embryo shows a c o n ti n u e d , p r o g r e s s i v e
d ev elo p m e n t o f t h e f o l l i c l e s w i t h i n t h e c o r d s . T h is s t a g e
F i g . 12. A c r o s s - s e c t i o n , marked 1 -----1 ' F i g . 10
th r o u g h t h e t h y r o i d g la n d o f a 35 mm. embryo show ing fenei
t r a t e d p l a t e s and c o r d s , x 150
QD, c o r d s
F P , f e n e s t r a t e d p l a t e s
LO, l o b u l e
F ig . 12
30
m arks t h e c lim a x o f th e d ev elo p m en t o f t h e p rim a ry f o l l i c l e s
and g i v e s e v id e n c e o f a new ty p e o f d ev elo p m e n t c h a r a c t e r
i z e d hy t h e b r e a k i n g up o f t h e c o r d s . In p l a c e s th e c o rd s
h a v e b r o k e n i n t o s h o r t s t r a n d s , a few s c a t t e r e d f o l l i c l e s
h av e b e e n s e g r e g a t e d , and i n o t h e r p l a c e s , m asses o f c e l l s
have b e e n form ed and a r e s u rro u n d e d by s tro m a . T h is c o n d i
t i o n i s fo u n d in t h e human g la n d o f 30 mm. s i z e a c c o r d i n g
to N o r r i s ( ’1 6 ) .
The 65 mm. embryo was s e c t i o n e d s a g i t t a l l y . The
f i r s t s e c t i o n s , w h ich w ere o u t from t h e s i d e o f t h e l o b e ,
i n c l u d i n g t i s s u e from t h e p e r i p h e r a l r e g i o n o n l y , show t h e
f o l l i c l e s to b e q.uite u n if o r m ly d i s t r i b u t e d th r o u g h o u t t h e
e n t i r e s e c t i o n . Some have w e ll- f o r m e d lu m in a , w h ile o t h e r s
a r e s o l i d s p h e r e s w hich g i v e a b e a d e d a p p e a ra n c e to t h e tw o-
c e l l e d c o r d s ( f i g . 1 3 ) . S e c t i o n s c u t th r o u g h a r e g i o n i n
th e c e n t r a l p o r t i o n o f t h e l o b e show t h a t th e g r e a t e r num
b e r o f f o l l i c l e s a r e l o c a t e d in th e p e r i p h e r a l r e g i o n ex
t e n d i n g a b o u t h a l f way to t h e c e n t e r . The c o n c l u s i o n may be
drawn t h a t t h e c e n t r a l p o r t i o n o f th e lo b e i s n o t a s a d
v a n c e d i n i t s d i f f e r e n t i a t i o n a s th e p e r i p h e r a l . T h is co n
f i r m s t h e b e l i e f o f A s c h o ff ( ’ 24) t h a t t h e c e n t r a l r e g i o n i s
c o m p a r a tiv e ly u n d i f f e r e n t i a t e d a t t h i s t im e .
C ords and some f o l l i c l e s e x te n d th r o u g h t h e isth m u s
o f t h i s embryo. T h is i s th e f i r s t tim e t h a t th e y have b e e n
o b s e rv e d i n t h a t r e g i o n . In th e 19 mm. embryo, i t w i l l be
F i g , 1 3 , A p h o to m ic ro g ra p h o f a s a g i t t a l s e c t i o n
t h r o u g h t h e t h y r o i d g la n d o f a 55 mm. h o r s e embryo show
i n g c o r d s c o n t a i n i n g f o l l i c l e s , a l s o a r e a s i n w hich t h e
c o r d s a r e d i s i n t e g r a t i n g , x 175
CJP F , c o rd c o n t a i n i n g f o l l i c l e s
D CD, d i s i n t e g r a t i n g c o r d s
SE , septum o f mesenchyme
Fig. IS
31
r e c a l l e d , th e l o b e s w ere c u t s a g i t t a l l y b u t t h e isth m u s
t r a n s v e r s e l y a s in t h i s s e r i e s . In t h e s e t r a n s v e r s e s e c
t i o n s t h e c e l l s w ere a r r a n g e d a s i n th e e a r l y p l a t e s , n o
w here showing t h e more a d v an ced dev elo p m en t o f th e l o b e s .
T h is would n o t be i n a c c o rd w i t h th e o b s e r v a t i o n s o f N o r r i s
( ’18) on th e human embryo, w here t h e p l a t e s and f o l l i c l e s
w ere more a b u n d a n t i n t h e isth m u s and i n t h e p a r t o f th e
l o b e s a d j o i n i n g th e is th m u s . I n t h e 35 mm. embryo, p l a t e s
w ere e v id e n t i n t h e is th m u s b u t n o t c o r d s ( f i g . 1 0 ) .
The c o n n e c ti v e t i s s u e s e p t a show a somewhat r e t i c u
l a r n a t u r e , some o f them a p p a r e n t l y b e a r i n g more f i b e r s th a n
o t h e r s . T o g e th e r w i t h t h e lo n g f i b e r s and l y i n g i n th e same
g e n e r a l d i r e c t i o n i n w hich t h e f i b e r s r u n , o c c u r a lm o st
s p i n d l e - s h a p e d n u c l e i , th e n u c l e i o f f i b r o b l a s t s o r co n n ec
t i v e t i s s u e c e l l s . A n o th e r ty p e o f c e l l s , f i x e d , u n d i f f e r
e n t i a t e d mesenchymal c e l l s w i t h f l a t t e n e d n u c l e i , a p p e a r i n
o r n e a r th e w a l l s o f t h e sm a ll b lo o d v e s s e l s w h ic h a r e
fo rm in g i n t h e c o n n e c t i v e t i s s u e s e p t a , a few s p h e r i c a l
c e l l s , s m a ll e r t h a n t h e parenchym al c e l l s o f th e g la n d and
more d e e p ly s t a i n e d , a p p e a r s i n g l y o r in s m a ll g ro u p s w i t h i n
t h e stro m a . T hese a r e c a l l e d ly m p h a c y te s by Maximow and
Bloom ( ’3 2 ) , b u t Cowdry ( ’34) c o n s i d e r s them a n o t h e r ty p e
o f u n d i f f e r e n t i a t e d mesenchymal c e l l s .
H orse em bryos from 64 mm. to 117 mm. i n l e n g t h .
32
T h is g ro u p o f em bryos w i l l be c o n s i d e r e d t o g e t h e r b e c a u s e
th e y c o v e r a p e r i o d o f r a p i d g ro w th and r e p r e s e n t p h a s e s in
a p r o g r e s s i v e develo p m en t c h a r a c t e r i z e d a t f i r s t by r e l a
t i v e l y few c o r d s , num erous s c a t t e r e d paren ch y m al c e l l s ,
g ro u p s o f c e l l s l o o s e l y c o n s t r u c t e d , and o n ly an o c c a s i o n a l
w e ll- f o r m e d f o l l i c l e ( f i g . 1 4 ) . L a t e r , t h e l o o s e l y con
s t r u c t e d g ro u p s o f c e l l s form s o l i d m asses i s o l a t e d w i t h i n
t h e stro m a , ( f i g . 1 5 ) . T hese g i v e r i s e to g ro u p s o f c e l l s
w hich e v e n t u a l l y form h o llo w f o l l i c l e s ( f i g . 1 6 ) .
The g l a n d in t h e 64 mm. embryo m e a su re s 854 m ic ro n s
in t o t a l l e n g t h and h a s m ig r a te d p o s t e r i o r w a r d u n t i l i t l i e s
d o r s o - l a t e r a l t o th e f i r s t two o r t h r e e c a r t i l a g i n o u s r i n g s
o f t h e t r a c h e a . I t e x te n d s d o r s a lw a r d t o w i t h i n a few mi
c r o n s o f th e e s o p h a g u s . The b r e a k i n g up o f t h e c o r d s , w hich
was b e g in n i n g i n t h e 55 mm, embryo, h a s c o n tin u e d u n t i l
t h e r e i s o n ly a n o c c a s i o n a l s u g g e s t i o n o f them . The c e l l s
i n p l a c e s a r e s t i l l l i n e d up i n more o r l e s s o f a row o r
colum n, b u t th e y a r e in d e p e n d e n t o f eac h o t h e r a s th o u g h
th e y had b e e n c o m p le te ly shaken a p a r t . H ere and t h e r e
th r o u g h o u t t h e g l a n d , g ro u p s o f c e l l s a r e r e a r r a n g i n g them
s e l v e s i n t o c l u s t e r s , some sm a ll and some l a r g e . R a r e ly i s
t h e r e any e v id e n c e o f f o l l i c l e s , many s e c t i o n s show ing none
a t a l l . When th e y do a p p e a r , th e y a r e fou nd i n t h e p e r i
p h e r a l r e g i o n n e a r t h e o u t e r b o u n d a r y . The p rim a ry f o l l i
c l e s fo u n d in th e c o r d s o f t h e g la n d i n t h e 55 mm. embryo
F i g . 1 4 . A p h o to m ic ro g ra p h o f a t r a n s v e r s e s e c t i o n
th r o u g h t h e t h y r o i d g la n d o f a 64 mm. embryo show ing a
c o m p le te d i s i n t e g r a t i o n o f c o r d s and f o l l i c l e s emd t h e ob
s c u r i t y o f t h e c o n n e c tiv e t i s s u e s e p t a , x 280
P i g , 14
F i g . 1 5 . A p h o to m ic ro g ra p h o f a t r a n s v e r s e s e c
t i o n t h r o u g h t h e t h y r o i d g la n d o f a 100 mm. embryo show
in g t h e r e o r g a n i z a t i o n o f t h e s c a t t e r e d c e l l s i n t o c e l l
m a s s e s , and th e r e a p p e a r a n c e o f t h e c o n n e c ti v e t i s s u e
s e p t a . X 280
C M, c e l l mass
g
H
0
Fig. 15
F i g . 1 6 . A p h o to m ic ro g ra p h o f a t r a n s v e r s e
s e c t i o n o f t h e t h y r o i d g la n d o f a 117 mm. embryo show
in g sm a ll s p h e r i c a l to s p h e r o i d a l f o l l i c l e s fo rm in g
from s o l i d c e l l m a sse s, x 280
P F , p r im a ry f o l l i c l e
m
4
M i
Pig. 16
33
h a v e , in th e 64 mm. s t a g e , a p p a r e n t l y become d i s i n t e g r a t e d
and a r e now b e g in n i n g th e p r o c e s s o f r e o r g a n i z a t i o n . The
c o n n e c ti v e t i s s u e s e p t a so c l e a r l y d e f i n e d by t h e c o r d s in
th e 55 mm. embryo a r e much o b s c u re d by t h e s c a t t e r e d c e l l s
e x c e p t w here th e y c o n t a i n c o a r s e r f i b e r s .
The 87 mm. s i z e shows t h e same l o o s e a rra n g e m e n t o f
t h e c e l l s i n t h e c l u s t e r s and i n s h o r t s t r a n d s . The lo o s e
c e l l s s c a t t e r e d th r o u g h o u t t h e g la n d mass a r e c o n s p ic u o u s ly
n u m ero u s. The f o l l i c l e s a r e in somev/hat l a r g e r num bers
th a n in th e 64 mm. s t a g e and a p p e a r in t h e c e n t r a l a s v/ell
a s i n th e p e r i p h e r a l r e g i o n . They a r e s p h e r i c a l in form ,
and t h e i r lu m in a a r e o n ly a few m ic ro n s in d i a m e t e r .
In th e 100 mm. embryo t h e g la n d shows a r a p i d p r o l i
f e r a t i o n o f c e l l s and a c o r r e s p o n d in g i n c r e a s e i n s i z e .
S o l i d m asses o f c e l l s a r e more n um ero u s, and hollov/ f o l l i
c l e s a r e i n c r e a s i n g i n number b u t s t i l l a r e n o t a b u n d a n t.
Some i n t h e p e r i p h e r a l r e g i o n show an i n c r e a s e i n s i z e o v e r
t h o s e o f t h e 87 mm. and o c c a s i o n a l l y , a lum en may be fo und
d e p a r t i n g from t h e t y p i c a l s p h e r i c a l form . Many s c a t t e r e d
c e l l s a r e s t i l l to be se e n e v e ry w h e re .
In t h e 108 mm. s t a g e t h e h o llo w f o l l i c l e s a r e n o t
y e t a s num erous a s t h e s o l i d m asses o f c e l l s . T h ere a r e
s l i g h t l y more o f them in t h e p e r i p h e r a l th a n i n t h e c e n t r a l
a r e a , an d , a s i n t h e 87 mm., th e y a r e l a r g e r i n t h a t r e g i o n
and f r e q .u e n tly have i r r e g u l a r l y form ed lu m in a . A re a s o f
34
paren ch y m al t i s s u e a r e s e p a r a t e d by r a t h e r b ro a d b a n d s o f
c o n n e c ti v e t i s s u e a r i s i n g , a p p a r e n t l y , from t h e c a p s u l e and
e x te n d in g in w a rd , g i v i n g a d e f i n i t e l o b u l a r a rra n g e m e n t to
th e g la n d t i s s u e . Each l o b e o f t h i s g la n d m e a su re s a b o u t
1890 m ic ro n s i n l e n g t h .
The g l a n d i n t h e 117 mm. embryo shov/s num erous sm a ll
s p h e r i c a l o r s p h e r o i d a l f o l l i c l e s w i t h lu m in a . They a r e
s t i l l n o t eq.ual i n number to t h e s o l i d m asses o f c e l l s . A
few f o l l i c l e s h av e g r e a t l y e lo n g a te d lu m in a and show e v i
de n ce o f a c o n s t r i c t i o n o r t h e f o r m a t io n o f a h o llo w bu d,
t h e lumen o f v/hich i s c o n tin u o u s w i t h t h a t o f t h e p a r e n t
f o l l i c l e .
The p e r i o d o f d ev elo p m e n t r e p r e s e n t e d by t h i s grou p
o f embryos r o u g h l y p a r a l l e l s t h a t i n t h e human betw een t h e
50 mm. and 86 mm. s i z e s a s d e s c r i b e d by N o r r i s .
H orse embryo 158 mm. in l e n g t h . T h is embryo shows
th e g l a n d g r e a t l y i n c r e a s e d in s i z e , i t s l e n g t h b e in g n o t
l e s s t h a n 2500 m ic r o n s . The d e v e lo p m e n t h e r e i s s i g n i f i
c a n t a s i t m arks a s t a g e w e l l ad v an c ed i n t h e f o r m a t io n o f
s e c o n d a ry f o l l i c l e s from p rim a r y f o l l i c l e s . The g e n e r a l
p i c t u r e i s one o f g r e a t c o m p le x ity o f form ( f i g . 1 7 ) . T h is
s t a g e i s v e r y s i m i l a r to t h e d e s c r i p t i o n and i l l u s t r a t i o n
by N o r r i s f o r t h e 86 mm. human em bryo. B o th t h e h o llo w and
s o l i d m asses o f p a ren ch y m al c e l l s a r e p r e s e n t th o u g h t h e
F i g . 1 7 . A p h o to m ic r o g r a p h o f a t r a n s v e r s e s e c t i o n
o f th e t h y r o id g la n d o f a 1 5 7 mm. embryo sh o w in g i r r e g u l a r
l y form ed f o l l i c l e s , and t h e fo r m a tio n o f se c o n d a r y f o l
l i c l e s b y t h e b u d d in g o f p r e e x i s t i n g f o l l i c l e s , x 600
B F , b u d d in g f o l l i c l e
I F , i r r e g u l a r f o l l i c l e
Fig. 17
35
s o l i d m asses s t i l l p r e d o m in a te . The s m a l l , s i n g l e , s p h e r
i c a l to s p h e r o i d a l f o l l i c l e s e v ery w h ere e v i d e n t in t h e 117
mm. embryo have i n c r e a s e d in s i z e , many o f them becom ing
q.uite l a r g e , and e x h i b i t i n g ex tre m e v a r i a b i l i t y in form .
A l l th r o u g h t h e g l a n d a r e e l o n g a t e d f o l l i c l e s show ing t h e
f o r m a t io n o f h o llo w o r s o l i d b u d s , a n d , i f t h e e l o n g a t i o n
i s e x c e s s i v e a c o n s t r i c t i o n n e a r th e c e n t e r may o c c u r , t h u s
fo rm in g s e c o n d a ry f o l l i c l e s by d i v i s i o n . O th e r f o l l i c l e s
a r e p r e s e n t w h ich do n o t show b u d d in g b u t w hich hav e i r r e g -
\Tlar sh a p e s o f v a r y i n g d e g r e e s o f c o m p le x ity .
F or t h e f i r s t tim e i n t h i s s e r i e s o f embryos i t i s
p o s s i b l e to f i n d v i s i b l e c o l l o i d w i t h i n t h e lu m in a o f some
o f th e f o l l i c l e s . These f o l l i c l e s , h o w ev er, a r e few in
number and w id e ly s c a t t e r e d . S in c e t h e r e i s no e v id e n c e ,
i n t h e m a t e r i a l s o f t h i s s tu d y o r i n t h e f i n d i n g s o f i n v e s
t i g a t o r s o f o t h e r mammals, t h a t t h e r e h a s b e e n a f l u i d o f
any n a t u r e s e c r e t e d by th e o t h e r a p p a r e n t l y empty f o l l i c l e s
o f y o u n g e r em bryos, i t may be c o n c lu d e d t h a t c o l l o i d d e v e l
o p s f o r th e f i r s t tim e in t h e h o r s e embryos o f a b o u t t h i s
s i z e . S e v e ra l f o l l i c l e s show a v a c u o le v /ith in t h e c o l l o i d .
H orse em bryos 180 mm. and 230 mm. i n 1 e n g t h . The
t h y r o i d g la n d i n t h e s e embryos a p p e a r i n some r e s p e c t s more
s im p le i n s t r u c t u r e t h a n t h a t o f t h e 158 mm. embryo. T here
a r e q _ u a n titie s o f s i n g l e , u n d i f f e r e n t i a t e d e p i t h e l i a l c e l l s
36
and many m asses o f them in t h e i n t e r f o l l i c u l a r s p a c e s . In
th e 180 mm. em bryo, t h e f o l l i c l e s a r e much more num erous
th a n in th e 158 mm. They v a ry from m in u te o n e s , 10 m ic ro n s
in d i a m e t e r to l a r g e o n e s , 45 m ic r o n s . The f o l l i c l e s a r e
c o n s p i c u o u s ly s p h e r i c a l o r s p h e r o i d a l in s h a p e . The i r r e g
u l a r i t y fo u n d in a l l f o l l i c l e s t h r o u g h o u t th e e n t i r e g l a n d
o f t h e 158 mm. embryo h a s d i s a p p e a r e d e x c e p t f o r an o c c a
s i o n a l one w hich may be e lo n g a te d o r may be in t h e p r o c e s s
o f fo rm in g a bud* The number o f f o l l i c l e s and t h a t o f s o l i d
i n t e r f o l l i c u l a r m a sse s i s a b o u t t h e same. C o l l o i d i s fou nd
in an i n c r e a s i n g number o f f o l l i c l e s and commonly c o n t a i n s
l a r g e v a c u o l e s , o f t e n s e v e r a l i n one f o l l i c l e . The p e r i p h
e r a l r e g i o n shows a m arked i n c r e a s e o v e r t h e c e n t r a l r e g i o n
in number and s i z e o f f o l l i c l e s a s w e l l a s in th e number o f
lu m in a f i l l e d w i t h c o l l o i d . T h is a g a i n shows th e advance in
d i f f e r e n t i a t i o n to b e a t t h e p e r i p h e r y o f th e g l a n d .
The g la n d i n t h e 230 mm. embryo d i f f e r s from t h a t in
t h e 180 mm. c h i e f l y i n s i z e o f f o l l i c l e s ( f i g . 1 8 ) . The
number h a s n o t i n c r e a s e d to any e x t e n t , b u t th e y have i n
c r e a s e d i n s i z e u n t i l th e l a r g e r o n e s m easure 130 m ic ro n s
i n d i a m e t e r . T h e i r shape i s e s s e n t i a l l y t h e same e x c e p t f o r
an o c c a s i o n a l b u d d in g f o l l i c l e , o r one much e lo n g a te d a s in
180 mm. s t a g e . T h ere a r e , h ow ever, many s m a ll , s p h e r i c a l
f o l l i c l e s p r e s e n t among th e l a r g e r o n e s . In b o t h embryos
th e c e l l s i n t h e w a l l s o f t h e f o l l i c l e s a r e co lum n ar i n
F i g . 1 8 . A p h o to m ic ro g ra p h o f a t r a n s v e r s e s e c
t i o n t h r o u g h t h e t h y r o i d g l a n d o f a 21 mm. embryo show ing
t h e r e g u l a r i t y i n t h e shape o f t h e f o l l i c l e s and an i n
c r e a s e i n th e s i z e o f some o f them . Many s m a ll f o l l i c l e s
and i n t e r f o l l i c u l a r c e l l s a r e a p p a r e n t b e tw e e n t h e l a r g e r
f o l l i c l e s . X 190
B F , b u d d in g f o l l i c l e
I C , i n t e r f o l l i c u l a r c e l l s
ss , septum
SM F, s m a ll f o l l i c l e s
V v a c u o le
-k • • » ' ^
£
Fig. 18
37
fo rm . Among t h e s e t y p i c a l f o l l i c u l a r c e l l s in th e w a l l o f
many f o l l i c l e s w hich c o n t a i n c o l l o i d may he fou nd one to
s e v e r a l c e l l s l a r g e r th a n t h e f o l l i c u l a r c e l l s ( f i g . 1 9 ) .
T hese c e l l s h a v e l a r g e , a lm o s t s p h e r i c a l n u c l e i and c l e a r
c y to p la s m . These n u c l e i do n o t s t a i n a s d e e p ly a s t h o s e o f
t h e f o l l i c u l a r c e l l s . T h is ty p e o f c e l l s h a s n o t b e e n
fo u n d i n t h e w a l l s o f any f o l l i c l e s e x c e p t th o s e c o n t a i n i n g
c o l l o i d . The a p p e a ra n c e o f t h e s e c e l l s s u g g e s t s t h e " o v o id ”
c e l l s d e s c r i b e d by B e n s ie y ( ’14) i n h i s s tu d y o f t h e t h y r o i d
o f t h e opposum; t h e " p a r a f o l l i c u l a r " c e l l s o f N on idez ( ’ 3 2 a ,
32b) i n t h e t h y r o i d o f t h e dog, and o f th e c a t r e s p e c t i v e l y ,
and o f Raymond (*3 2) i n th e r a b b i t ; and th e " m a c r o th y r o c y te s "
fo u n d by Z e c h e l ( ’33) i n t h e human.
The e n t i r e g la n d in th e 230 mm. h o r s e embryo i s
b ro k e n up i n t o l o b u l e s s e p a r a t e d by s e p t a o f a f i b r o u s n a
t u r e c o n t a i n i n g many b lo o d v e s s e l s and lymph s i n u s o i d s .
T hese s e p t a e x te n d from t h e c a p s u l e , w h ich c o n t a i n s many
c o a r s e f i b e r s and h a s a much d e n s e r s t r u c t u r e t h a n th e
s e p t a .
A d u lt h o r s e . The l o b e s o f t h e t h y r o i d g l a n d i n t h e
a d u l t h o r s e have a b o u t th e form and s i z e o f a plum . Each
l o b e i s a b o u t 4 cm. lo n g and 2 .5 t o 3 cm. w id e . They l i e
d o r s o - l a t e r a l to t h e f i r s t t h r e e c a r t i l a g i n o u s r i n g s o f t h e
t r a c h e a . The is th m u s , w i t h t h e e x c e p t i o n o f some c o n n e c ti v e
Fig. 19. A camera lue id a sketch of a f o l l i c l e in
the thyroid of the 180 mm. embryo showing la rg e c e l ls
w ith sp h e ric a l n u c le i and c le a r cytoplasm among the t y p i
cal i n t e r f o l l i c u l a r c e l l s , x 150
CO, c o llo id
FC, f o l l i c u l a r c e ll
LC, la rg e c e ll
VA, vacuole
m m
1 •
38
t i s s u e , h a s d i s a p p e a r e d b e f o r e t h e a d u l t s t a g e o f d e v e l o p
ment i s r e a c h e d , l e a v i n g no c o n n e c ti o n o f g l a n d u l a r t i s s u e
b e tw e e n t h e l o b e s .
T r a n s v e r s e s e c t i o n s o u t from d i f f e r e n t r e g i o n s o f
th e l o b e s show many v e r y l a r g e f o l l i c l e s , some m e a su rin g
700 m ic ro n s i n l e n g t h and 550 m ic ro n s in w id th . In g e n e r a l
t h e shap e o f t h e s e f o l l i c l e s i s s p h e r o i d a l , b u t t h e f o l l i c
u l a r v/all shows i r r e g u l a r i t y o f form i n s t e a d o f t h e sm ooth
b o u n d a ry c h a r a c t e r i s t i c o f t h e f o l l i c l e s in t h e 230 mm.
embryo ( f i g . 2 0 ) . Betw een t h e s e l a r g e f o l l i c l e s a r e l a r g e
and s m a ll m a sse s o f i n t e r f o l l i c u l a r c e l l s i n w hich a r e
b e i n g d i f f e r e n t i a t e d num erous s m a ll f o l l i c l e s o f v a r y i n g
s i z e s and s h a p e s . S in g le u n d i f f e r e n t i a t e d c e l l s , so common
i n t h e em bryonic s t a g e s o f d e v e lo p m e n t, a r e s t i l l a p p a r e n t
i n t h e a d u l t g l a n d . The e p i t h e l i a l c e l l s i n t h e w a l l s o f
t h e f o l l i c l e s a r e low co lum n ar c e l l s w i t h s p h e r i c a l n u c l e i .
The lu m in a a r e ev eryw here f i l l e d w i t h c o l l o i d , w hich s t a i n s
more d e e p ly th a n t h a t fou nd i n t h e 180 mm. and 230 mm.
s t a g e s . O c c a s i o n a l l y v a c u o l e s a r e fo u n d w i t h i n t h e c o l l o i d ,
b u t i n t h i s m a t e r i a l th e y a r e n o t a s a b u n d a n t a s i n t h e 230
mm. g l a n d . The l a r g e c e l l s v /ith s p h e r i c a l n u c l e i and c l e a r
c y to p la s m , w h ic h w ere fo u n d i n t h e f o l l i c u l a r w a ll o f t h e
em bryonic t h y r o i d s , have n o t b e e n fo u n d i n t h e a d u l t m a te
r i a l i n t h i s s e r i e s .
The c o n n e c ti v e t i s s u e s e p t a , w h ich o c c u r b e tw e e n th e
F i g . 20. A p h o to m ic ro g r a p h o f a t r a n s v e r s e s e c t i o n
t h r o u g h a p o r t i o n o f t h e t h y r o i d g la n d o f an a d u l t h o r s e
show ing l a r g e and s m a ll f o l l i c l e s w i t h low e p i t h e l i a l
c e l l s i n t h e f o l l i c u l a r w a l l s , c l u s t e r s o f i n t e r f o l l i c u
l a r c e l l s and l o o s e c e l l s , and f i b r o u s s e p t a , x 190
I C, i n t e r f o l l i c u l a r c e l l s
L F , l a r g e f o l l i c l e
SE , septum
S F , sm a ll f o l l i c l e s
V . v a c u o le
I »
P ig . 20
39
lo'b'ules o f t h e g l a n d , a r e c o m p a r a tiv e ly "broad, h a v in g t h e
a p p e a ra n c e o f s t r o n g f i h r o u s h a n d s t h a t e n c l o s e l a r g e r a r
t e r i e s , v e i n s , and lymph s i n u s o i d s . Many sm a ll v e s s e l s a r e
foim d i n t h e i n t e r f o l l i c u l a r t i s s u e among t h e sm a ll f o l l i
c l e s and n e s t s o f c e l l s . The f i n d i n g s i n t h e s tu d y o f
t h i s a d u l t g la n d p a r a l l e l th o s e o f A rx ( ’ 28) f o r t h y r o i d s
i n a d u l t h o r s e s b e tw e e n 5 and 15 y e a r s o f a g e .
V. DISCUSSION
In t h e 5 mm. h o r s e emhryo t h e a n la g e o f t h e t h y r o i d
h a s become c o n s t r i c t e d to form a t u b e , and e x h i b i t s t h e
c r a n i o - c a u d a l d ev elo p m en t c h a r a c t e r i s t i c o f a l l v e r t e b r a t e s .
I t i s i m p o s s ib le to s t a t e j u s t when t h e a n la g e o f th e t h y
r o i d g la n d in th e h o r s e f i r s t o c c u r s . However, t h e e x t e n t
o f i t s d e v elo p m e n t in t h e 5 mm. embryo would i n d i c a t e t h a t
i t a p p e a r s a s e a r l y in th e h o r s e a s in t h e human. A c c o rd
in g to Maximow and Bloom ( ’ 3 4 ) , i t h a s b e en o b s e rv e d in
human embryos o f 1 .3 7 mm. The s i z e o f t h e o p e n in g i n t h e
f l o o r o f t h e p h a ry n x , w h ich m arks t h e b o u n d a ry o f t h e
a n l a g e , i s r e l a t i v e l y l a r g e and h a s a d e p th o f n o t more
t h a n 20 m ic ro n s b e f o r e i t n a rr o w s i n t o th e s t a l k e d t u b e r -
culum . A c c o rd in g to t h i s , t h e a n la g e i s a ’’r a t h e r e x t e n s i v e
b u t s h a llo w é v a g i n a t i o n ” a s i n t h e human ( N o r r i s ’18) .
A f t e r an i n v e s t i g a t i o n o f a l a r g e number o f human
em bryos N o r r i s fo u n d t h a t t h e t h y r o i d g la n d may t a k e one o f
t h r e e c o u r s e s o f d e v elo p m e n t f o l l o w i n g t h e a n la g e s t a g e ;
n a m e ly , a s o l i d g lo b o s e bud c o n n e c te d t o t h e p h a ry n x by a
s h o r t s o l i d s t a l k , a bud su sp e n d e d by a h o llo w s t a l k , o r a
b i l o b e d s t r u c t u r e , g i v i n g t h e a p p e a ra n c e o f a d o u b le g la n d
i n c l o s e c o n n e c ti o n w i t h t h e p h a ry n x . W hether o r n o t a l l o f
t h e s e t y p e s o c c u r i n h o r s e em bryos, i t i s i m p o s s ib le t o s a y ,
b u t t h e embryo s t u d i e d u n q u e s t i o n a b l y c o r r e s p o n d s to t h e
d e s c r i p t i o n o f t h e seco nd t y p e . The s t a l k w ith i t s lum en
41
e x te n d s p o s t e r i o r w a r d f o r a d i s t a n c e o f a b o u t 50 m ic ro n s
and t h e r e t e r m i n a t e s i n a mass o f p r o l i f e r a t i n g e p i t h e l i a l
c e l l s . These c e l l s a r e d e s t i n e d to form t h e p r i m o r d i a l
p l a t e o f th e g l a n d . In t h e 6 mm. h o r s e t h i s mass o f c e l l s
h a s become s e p a r a t e d from t h e f l o o r o f t h e p h a ry n x , t h e
s t a l k s e v e r i n g n e a r i t s p o i n t o f a tt a c h m e n t to t h e p l a t e .
A c o u p le o f p y r a m i d a l - l i k e p r o j e c t i o n s , e x te n d in g c e p h a la d
from t h e a n t e r i o r s u r f a c e o f t h e p l a t e , may be t h e c u t edges
o f l o n g i t u d i n a l s e c t i o n s t h r o u g h th e b a s e o f t h e t u b e . In
t h i s p a r t i c u l a r embryo t h e o n ly e v id e n c e o f t h e l o c a t i o n o f
t h e fo rm e r t u b e , " th e t h y r e o g l o s s a l d u c t , ” i s a few s c a t t e r e d
e p i t h e l i a l c e l l s i n t h e mesenchyme l y i n g b e tw ee n t h e p l a t e
and t h e f l o o r o f t h e p h a ry n x . I n th e 9 mm. em bryo, how ever,
a p o r t i o n o f t h e a n t e r i o r end o f t h e d u c t i s fo u n d s t i l l a t
t a c h e d , and e x te n d in g c a u d a d . T h is re m n a n t o f t h e e a r l y
d u c t i s known a s t h e "C an al o f H i s . ” The p l a t e i n t h i s em
b ry o a l s o e x h i b i t s s h o r t l o b e - l i k e p r o j e c t i o n s e x te n d in g
from i t s c e p h a l i c s u r f a c e . T hese may be t h e r e s u l t o f an
i r r e g u l a r l i n e o f s e p a r a t i o n from t h e d u c t . From t h e s e two
i l l u s t r a t i o n s i t i s e v i d e n t t h a t p o r t i o n s o f t h e t h y r e o g l o s
s a l d u c t may p e r s i s t i n p o s t n a t a l l i f e i n t h e h o r s e a s w e ll
a s i n t h e human, i n t h e form o f a c a n a l a t t a c h e d to t h e
f l o o r o f t h e p h a ry n x , a p y ra m id a l lo b e o f t h e g l a n d , o r a s
s c a t t e r e d m asses o f g l a n d u l a r c e l l s in th e c o n n e c ti v e t i s s u e
b e tw e e n th e p h a ry n x and t h e l o b e s o f t h e g l a n d .
42
A s tu d y o f th e shape &md a rr a n g e m e n t o f t h e c e l l s
w i t h i n t h e p r i m o r d i a l p l a t e d e s c r i b e d f o r t h e 6 mm. h o r s e
embryo r e v e a l s a p i c t u r e re m a rk a b ly s i m i l a r to t h e h i s t o l o
g i c a l s t r u c t u r e o f t h e c o r r e s p o n d i n g e a r l y s t a g e i n th e h u
man. The shap e o f t h e n u c l e i o f t h e c e l l s ; t h e m asses o f
c h r o m a tin , v /ith t h e i r deep s t a i n i n g p r o p e r t y ; t h e c l e a r c y
to p la s m , u n l i m i t e d by c e l l b o u n d a r i e s ; and t h e a rra n g e m e n t
o f t h e c e l l s w i t h i n th e p l a t e a r e i d e n t i c a l f o r t h e s e two
v e r t e b r a t e s . In th e d e s c r i p t i o n o f t h e p l a t e found in th e
human N o r r i s s t a t e s :
No c e l l b o u n d a r i e s a r e fo u n d i n t h e e a r l i e s t mem
b e r s o f t h e s e r i e s . The c y to p la s m h a s a c l e a r , a lm o s t
h y a l i n e a p p e a ra n c e and o n ly i n f r e q u e n t l y shows a v e r y
few f i n e s c a t t e r e d g r a n u l e s . The n u c l e i a r e f a i r l y
t y p i c a l . They a r e l a r g e o v o i d a l b o d i e s h a v in g v e r y
d i s t i n c t n u c l e a r m em branes. In g e n e r a l , t h e n u c l e i
a r e so a r r a n g e d t h a t t h e i r l o n g a x e s a r e n e a r l y p e r
p e n d i c u l a r to t h e s u r f a c e s o f t h e a n l a g e . Each n u
c l e u s c o n t a i n s t h r e e o r f o u r l a r g e sm ooth chi*omatin
b l o c k s w h ich a r e p la c e d in an a lm o s t s t r u c t u r e l e s s
k a ry o p la s m and l i e e i t h e r i n a p p o s i t i o n w i t h t h e
n u c l e a r membrane o r a p p a r e n t l y f r e e i n t h e n u c l e a r
s a p .
The w r i t e r i n a s e a r c h o f t h e l i t e r a t u r e on t h e h i s
t o g e n e s i s o f t h e t h y r o i d g l a n d , d o e s n o t f i n d t h e d e t a i l s o f
s t r u c t u r e in t h e o r i g i n a l p l a t e d e s c r i b e d by t h e s e i n v e s t i
g a t o r s , f o r any b u t th e human.
B etw een t h e 6 mm. and 13 mm. s t a g e s o f d e v elo p m e n t
in t h i s s e r i e s o f h o r s e em bryos, c e l l p r o l i f e r a t i o n o c c u r s
w hich m a t e r i a l l y i n c r e a s e s t h e s i z e o f t h e p l a t e . I t r e
m ains a s i n g l e , s o l i d mass o f e p i t h e l i a l c e l l s u n t i l t h e
43
13 mm. s t a g e . H ere t h e h i l o h e d n a t u r e o f t h e g la n d i s a p
p a r e n t f o r t h e f i r s t t im e . In t h e human i t o c c u r s b e f o r e
t h e s e p a r a t i o n o f t h e p l a t e from t h e p h a ry n x . A v e r y few
m in u te , s l i t - l i k e c a v i t i e s , such a s N o r r i s fo u n d i n human
em bryos o f a b o u t 7 mm., o c c u r f o r t h e f i r s t tim e i n t h e 13
mm. s t a g e . These c a v i t i e s a r e c o m p le te ly e n c lo s e d w i t h i n
t h e body o f th e g l a n d . The w r i t e r h a s f o llo w e d t h e d e v e l o p
ment o f t h e c a v i t i e s i n t h e h o r s e and f i n d s t h a t i t p a r a l l e l s
v e r y c l o s e l y t h a t i n t h e human. The c a v i t i e s grov/ from
t h e s e m in u te s l i t s to o p e n in g s o f l a r g e s i z e by c o n f lu e n c e
w i t h n e i g h b o r i n g c a v i t i e s , and e v e n t u a l l y , th e y open to th e
e x t e r i o r fo rm in g a c h a n n e l th r o u g h w hich t h e v a s c u l a r m esen
chyme g a i n s a c c e s s to t h e in n e r - m o s t r e g i o n s o f t h e g l a n d
m ass. T h is p r o c e s s o f d e v e lo p m e n t c o n t i n u e s u n t i l t h e en
t i r e g la n d h a s b e e n c o n v e r t e d i n t o a com plex o f c o r d s two
c e l l s i n t h i c k n e s s . N o r r i s ( ’1 7 , ’18) r e p o r t e d t h e s e c a v
i t i e s fo u n d i n S q u a lu s a c a n t h i a s embryos and s t a t e s t h a t
t h e tim e o f t h e i r a p p e a ra n c e c o r r e s p o n d s " e x a c t l y ” to t h a t
i n t h e human. He h a s a l s o made a c a s u a l s tu d y o f th e p i g e o n ,
s h e e p , d o g, p i g , and r a b b i t and fo u n d s i m i l a r c a v i t i e s i n
th e t h y r o i d o f e a c h . B ut G-odwin ( ’3 6 ) , in h i s s tu d y o f t h e
t h y r o i d o f t h e dog, f i n d s no i n t r a g l a n d u l a r c a v i t i e s vrhioh
open to t h e e x t e r i o r and p e r m it t h e i n v a s i o n o f m esenchyme.
He f i n d s , i n s t e a d , a p r e c o c i o u s b r a n c h i n g from t h e o r i g i n a l
t h y r o i d p l a t e , w h ich a p p a r e n t l y o b v i a t e s t h e n e c e s s i t y f o r
44
su c h a m echanism . T hese b r a n c h e s a r e e v e n t u a l l y t r a n s
form ed i n t o p l a t e s two c e l l s t h i c k , from w h ich f o l l i c l e s
w i l l d e v e lo p . H is f i n d i n g s w ould c o n t r i b u t e e v id e n c e to
t h e f a c t t h a t t h e r e i s v a r i a t i o n in t h e f o r m a t i o n o f t h e
c o r d s o r p l a t e s from w h ich t h e p rim a ry f o l l i c l e s a r i s e .
N o r r i s , in an a t t e m p t to i n t e r p r e t t h e s i g n i f i c a n c e o f
t h e s e i n t r a g l a n d u l a r s p a c e s , s u g g e s t s two h y p o t h e s e s . He
s t a t e s , " I t m ig h t be th o u g h t t h a t t h e im m ed iate p u rp o s e and
s i g n i f i c a n c e o f t h e s e c a v i t i e s i s to be fou nd i n t h e fo rm a
t i o n o f t w o - c e l l e d p l a t e s from w h ich t h e f o l l i c l e s a r e l a t e r
to be d e r i v e d . On t h e o t h e r h a n d , i f t h e v e r t e b r a t e t h y
r o i d i s th e p h y l o g e n e t i c r e p r e s e n t a t i v e o f a t r u e e x t e r
n a l l y s e c r e t i n g g l a n d i t m ig h t be s u g g e s te d t h a t t h e s e
c a v i t i e s a p p e a r i n r e s p o n s e to a te n d e n c y to r e p r o d u c e th e
a n c i e n t lumen o r d u c t o f t h e a n c e s t r a l g l a n d . " G-odwin
t h i n k s t h e f i r s t o f t h e two s u g g e s t i o n s i s t h e more s a t i s
f a c t o r y i n t e r p r e t a t i o n . In th e h o r s e embryos s t u d i e d th e
f a c t t h a t c a v i t i e s do n o t form u n t i l some tim e a f t e r th e
s e p a r a t i o n o f t h e g la n d from t h e t h y r e o g l o s s a l d u c t w ould
a p p e a r to d i s c r e d i t t h e t h e o r y o f t h e i r p h y l o g e n e t i c
o r i g i n from t h e t h y r e o g l o s s a l d u c t . The d e v e lo p m e n t o f t h e
c a v i t i e s and t h e s im u lt a n e o u s b r e a k i n g up o f t h e p l a t e
l e a d s th e w r i t e r to c o n c lu d e t h a t t h e f i r s t i n t e r p r e t a t i o n
i s t h e more p l a u s i b l e .
T here i s a s i g n i f i c a n t d e p a r t u r e o f t h e manner o f
45
d e v e lo p m e n t in t h e t h y r o i d g l a n d o f t h e h o r s e from t h a t i n
t h e human a s c o n c e r n s th e d e r i v a t i o n o f t h e p rim a ry f o l l i
c l e s . N o r r i s ( ’1 6 ) , by r e c o n s t r u c t i o n m eth o d s, c o n c lu d e d
t h a t p rim a r y f o l l i c l e s i n t h e human a r i s e d i r e c t l y from
f e n e s t r a t e d e p i t h e l i a l p l a t e s , l o n g i t u d i n a l l y a r r a n g e d .
He c la im s t h a t w hat a p p e a r i n s e c t i o n s to be c o r d s a r e
i l l u s i o n s i n t h e g r e a t m a j o r i t y o f c a s e s . In t h i s i n v e s
t i g a t i o n s e c t i o n s o f h o r s e em bryos, i n t h e l a t e r s t a g e s o f
p r e f o i l i c u l a r d e v e lo p m e n t, have b e e n c u t t r a n s v e r s e l y ,
l o n g i t u d i n a l l y , and s a g i t t a l l y . A s tu d y o f s e c t i o n s i n
a l l t h r e e p l a n e s f a i l e d to r e v e a l t h e c o n t i n u i t y o f form
b e tw e e n s e c t i o n s w hich sh o u ld a p p e a r i f a p l a t e , e x te n d in g
i n one d i r e c t i o n f o r any d i s t a n c e , w ere c u t a t r i g h t a n g l e s
to i t s s u r f a c e . T h is f a c t c a u s e d d o u b t to a r i s e a s to t h e
f o r m a t i o n o f t h e t'w o -c e lle d p l a t e s w h ich N o r r i s fo und in
t h e human t h y r o i d . The r e c o n s t r u c t i o n o f one o f t h e l o b e s
o f t h e g la n d i n t h e 35 mm. em b ry o, w h ich was n e a r th e c u l
m in a t io n o f t h i s p r o c e s s o f c o rd f o r m a t i o n , c o n firm e d t h e
d o u b t. The model shoves c o n c l u s i v e l y t h a t , in t h e t h y r o i d
o f t h e h o r s e , t h e o r i g i n o f p rim a ry f o l l i c l e s i s t h e much
b r a n c h e d , t w o - c e l l e d c o r d s w h ich e x te n d in a l l d i r e c t i o n s
r a t h e r t h a n th e l o n g i t u d i n a l l y a r r a n g e d , t v m - c e l l e d p l a t e s
d e s c r i b e d by N o r r i s . S a n d e rs ( ’ 3 5 ) , in h i s s tu d y on
U r o d e le s , f i n d s t h e p rim a ry f o l l i c l e s d e v e lo p from l o n g i
t u d i n a l c e l l s t r i n g s o r co lu m n s, w h ile Godwin (’ 36) f i n d s
46
t h a t t h e c e l l c o r d s , w hich b r a n c h o f f from t h e p r i m o r d i a l
p l a t e i n t h e d og , a r e t r a n s f o r m e d i n t o p l a t e s two c e l l s in
t h i c k n e s s , w hich i n t u r n g i v e r i s e to t h e p r im a ry f o l l i c l e s .
The f i n d i n g s l e a d to t h e c o n c l u s i o n t h a t t h e r e i s v a r i a t i o n
among v e r t e b r a t e s , even among mammals, a s to t h e g e n e s i s o f
t h e s e f i r s t f o l l i c l e s .
I t h a s n o t b e e n p o s s i b l e to make a th o r o u g h s tu d y o f
t h e p r o c e s s e s in v o lv e d i n t h e a rra n g e m e n t and grov/th o f th e
e p i t h e l i a l c e l l s w hich e n t e r i n t o th e f o r m a t io n o f a f o l l i c l e
w i t h i n a c o r d . T h is i s due to t h e p o o r c o n d i t i o n o f t h e 30
mm. s e r i e s and to th e t h i c k n e s s o f t h e s e c t i o n s i n th e 35 ram.
em bryo. However, a few e a r l y f o l l i c l e s w hich a r e fo u n d to
be fo rm in g w i t h i n t h e c o r d s o f t h e 21 mm. s t a g e ( f i g . 9) show
a r e a r r a n g e m e n t o f t h e c e l l s a s p i c t u r e d by N o r r i s ( ’16) in
t h e human, and among t h e s e c e l l s a r e some w i t h m i t o t i c f i
g u r e s . A few c e l l s move away from t h e s u r f a c e o f t h e p l a t e
on e i t h e r s id e and t u r n a t an a n g le to t h e i r o r i g i n a l p o s i
t i o n , l e a v i n g a s l i g h t i n d e n t a t i o n in t h e s u r f a c e o f t h e
p l a t e . B e ca u se t h e s e o b s e r v a t i o n s have b e e n l i m i t e d t o so
few i l l u s t r a t i o n s , i t c a n n o t be s a i d w i t h c e r t a i n t y t h a t th e
s t e p s in v o lv e d a r e e n t i r e l y t h e same f o r b o t h v e r t e b r a t e s .
The p rim a ry f o l l i c l e s a r e n o t a b u n d a n t w i t h i n t h e c o r d s a t
any tim e , th o u g h many o f t h e c o r d s in t h e 55 mm. s t a g e con
t a i n enough o f them to g i v e t h e c h a r a c t e r i s t i c a p p e a ra n c e o f
a b e a d e d c h a in d e s c r i b e d f o r t h e human and f o r o t h e r a n im a ls .
47
The b r e a k i n g up o f t h e c o r d s m arks a n o t h e r s t r i k i n g
d i f f e r e n c e b e tw ee n t h e p r o g r e s s i v e d e v elo p m e n t o f t h e t h y
r o i d g la n d i n t h e h o r s e and t h a t fo u n d in th e human and i n
o t h e r a n im a ls d e s c r i b e d i n l i t e r a t u r e . A c c o rd in g t o N o r r i s
( ’16) and to e a r l i e r o b s e r v e r s , t h e f o l l i c l e s a r e s e p a r a t e d
from t h e p l a t e s o r c o r d s e i t h e r by b e in g f o r c e d o u t from t h e
row i n w h ich th e y a r e form ed by i n c r e a s e d p r e s s u r e due t o an
i n c r e a s e i n t h e number o f c e l l s b e tw e e n t h e i n d e n t a t i o n s o r
by a n in g ro w th o f m esenchymal t i s s u e b e tw e e n t h e f o l l i c l e s .
The m a t e r i a l s u s e d i n t h i s i n v e s t i g a t i o n o f t h e h o r s e show
no su c h s e p a r a t i o n o f f o l l i c l e s fro m t h e c o r d s . T here o c c u r s
a c o m p le te d i s s o c i a t i o n o f t h e c e l l s w i t h i n th e c o r d s and
w i t h i n t h e f o l l i c l e s t h e m s e l v e s . T h is i s t h e p i c t u r e p r e s e n
t e d i n t h e e n t i r e g la n d o f t h e 64 ram. em bryo. In t h e embryos
t h a t f o l l o w , (87 mm., 100 mm., 108 mm., 117 mm.), t h e r e i s
a g r a d u a l , p r o g r e s s i v e r e a s s o c i a t i o n o f t h e s e d i s c o n n e c t e d
c e l l s ; f i r s t , i n t o l o o s e l y c o n s t r u c t e d g r o u p s , t h e n , i n t o
d e n s e r m a s s e s , and f i n a l l y , i n t o m a sse s w hich hav e a c q u i r e d
a lu m en . The l a t t e r a r e q u i t e a b u n d a n t in t h e 117 ram. s t a g e .
S e c o n d ary f o l l i c l e s a r i s e fro m t h e s e r e c o n s t r u c t e d
p r im a r y f o l l i c l e s th r o u g h t h e p r o c e s s o f t h e f o r m a t io n o f
b u d s , b o t h s o l i d and h o llo w , a n d , o c c a s i o n a l l y , w here f o l l i
c l e s hav e g r e a t l y e l o n g a t e d , by c o n s t r i c t i o n . T h ere i s no
e v id e n c e i n t h i s m a t e r i a l o f a f u s i o n o f f o l l i c l e s a s r e
p o r t e d in t h e c a s e o f U r o d e le s , and i n t h e c h i c k a s d e s -
48
c r i b e d by S a n d e rs ( ’35) and H op kin s ( ’35) r e s p e c t i v e l y .
S t r u c t u r e s , show ing a m arked d e g re e o f i r r e g u l a r i t y , a re b e
l i e v e d to be due t o e x c e s s i v e g ro w th w h ich h a s l e a d to a
h i g h d e g re e o f c o m p l e x i t y . The o r i g i n o f s e c o n d a ry f o l l i
c l e s in th e human g l a n d , by t h e f o r m a t io n o f b o t h s o l i d and
h o llo w b u d s , and u n d e r c e r t a i n c o n d i t i o n s , by c o n s t r i c t i o n ,
h a s b e e n s t u d i e d , and c o n firm e d by many i n v e s t i g a t o r s •
Among t h e s e i n v e s t i g a t o r s a r e N o r r i s ( ’1 6 ), W ilso n ( ’27,
’ 28). The l a t t e r b a s e d h i s c o n c l u s i o n s w h o lly upon h i s r e
c o n s t r u c t i o n s , w h i l e J a c k s o n ( ’31) and R i e n h o f f ( ’29) u se d
a m ethod o f d i s s o c i a t i o n by m a c e r a ti o n and m ic r o - d i s s e c t i o n
and w ere a b le to d e m o n s tr a te t h e same c o n d i t i o n s from t h e
f o l l i c l e s th e m s e lv e s . H i l l ( ’35), i n h i s s tu d y o f t h e t h y
r o i d g l a n d o f Amia c a l v a , r e p o r t s se c o n d a ry f o l l i c l e s
a r i s i n g by d i v i s i o n b u t c l a i m s t h a t no s o l i d o u tg r o w th s o f
c e l l s from p rim a ry f o l l i c l e s v/ere o b s e r v e d . S a n d e rs ( ’ 35)
on U r o d e le s , and H opk ins ( ’ 35) on t h e c h i c k , c la im t h a t
grov/th o c c u r s by f u s i o n o f p rim a ry f o l l i c l e s r a t h e r t h a n by
b u d d in g .
The f a c t t h a t c o l l o i d makes i t s a p p e a ra n c e w i t h t h e
a d v e n t o f t h e p e r i o d o f s e c o n d a r y f o l l i c u l a r d e v e lo p m e n t
w ould seem to j u s t i f y t h e c o n c l u s i o n t h a t t h e g la n d i s b e
g i n n i n g i t s s e c r e t o r y f u n c t i o n a t t h i s t i m e . A n o th e r i n
t e r e s t i n g f e a t u r e c h a r a c t e r i z i n g t h i s p e r i o d o f d e v elo p m e n t
i s t h a t among t h e t y p i c a l co lu m n ar c e l l s t h a t fo rm t h e w a l l
49
o f th e f o l l i c l e , o c c u r c e l l s o f a d i f f e r e n t sh ap e and ap
p e a r a n c e . T hese h a v e b e e n d e s c r i b e d i n t h e d i s c u s s i o n on
t h e 180 mm. and 230 mm. s t a g e s . As h a s a l r e a d y b e e n p o i n t e d
o u t, t h e s e c e l l s a r e s i m i l a r to t h e " o v o id ” c e l l s in th e
opossum , B e n s le y ( ’14); to t h e " p a r a f o l l i c u l a r " c e l l s in t h e
dog and c a t , N o n id ez ( ’32), and i n t h e r a b b i t , Raymond
( ’32); and to t h e " l a r g e " c e l l s in t h e d o g , and to th e
" m a c r o th y r o c y te s " i n t h e human, Z e c h e l ( ’32, ’33). Each o f
t h e s e i n v e s t i g a t o r s a s s o c i a t e t h e s e c e l l s w i t h t h e s e c r e
t o r y f u n c t i o n o f t h e f o l l i c l e s . N onid ez c la im s t h a t th e
" p a r a f o l l i c u l a r c e l l s " a r e a secon d e p i t h e l i a l component o f
t h e t h y r o i d g l a n d . He e x p l a i n s t h a t t h e y a r i s e by a p e c u
l i a r p r o c e s s o f t r a n s f o r m a t i o n o f c e r t a i n e le m e n ts i n th e
f o l l i c u l a r e p i t h e l i u m and p o i n t s o u t t h a t t h e s e t r a n s f o r m a
t i o n s a r e fo u n d i n a l l f o l l i c l e s c o n t a i n i n g c o l l o i d and
h a v e b e e n o b s e r v e d to m ig r a te fro m t h e f o l l i c u l a r w a l l i n t o
t h e i n t e r f o l l i c u l a r s p a c e s . He b e l i e v e s t h a t th e y a re
e n d o c r in e in n a t u r e . Z e c h e l fo u n d l a r g e c e l l s , c o r r e s p o n d
in g to t h e d e s c r i p t i o n o f t h e p a r a f o l l i c u l a r c e l l s , i n t h e
i n t e r f o l l i c u l a r s p a c e s and i n t h e f o l l i c l e w a l l , and he
a l s o fo u n d t h a t , v /h atev e r t h e i r l o c a t i o n , th e y w ere a s s o
c i a t e d w i t h c o l l o i d . He b e l i e v e s t h a t a f o l l i c l e i s m e re ly
a p h a se i n a m e ta m o rp h o s is , w hich a l t e r n a t e s b e tw e e n th e
f o l l i c l e on one end and t h e i n t e r f o l l i c u l a r c e l l g ro u p on
t h e o t h e r , and t h a t t h e s e s p e c i a l c e l l s a r e a c t i v e i n t h e
50
f o r m a t i o n o f new f o l l i c l e s , i n t h e s e c r e t i o n o f c o l l o i d ,
and p e r h a p s , t h a t th e y h a v e so m e th in g to do w i t h t h e b r e a k
in g down o f th e f o l l i c l e s . Cowdry s u g g e s t s t h a t t h e s e c e l l s
d e s c r i b e d by t h e v a r i o u s i n v e s t i g a t o r s , may b e p h a s e s in t h e
s e c r e t o r y c y c l e t h r o u g h w h ic h t h e " c h i e f " o r t y p i c a l f o l l i c
u l a r c e l l p a s s e s * I t i s th e o p i n i o n o f t h e w r i t e r , b a s e d
on t h e s tu d y o f th e h o r s e , t h a t Cowdry’ s e x p l a n a t i o n i s th e
m ost s a t i s f a c t o r y , b e c a u s e t h e c h i e f c e l l s form t h e e n t i r e
w a l l o f t h e h o llo w v e s i c l e , and b e c a u s e now here i n t h e w a l l
i s t h e r e any e v id e n c e o f a new ty p e o f c e l l f o r m in g . In
t h e s e e a r l y embryos no f o l l i c l e s h a v e b e e n fo u n d w here a
c e l l o f t h i s ty p e i s p u s h in g i t s way in betv;een t h e f o l l i c
u l a r c e l l s from t h e i n t e r f o l l i c u l a r s p a c e s . I t w ould seem
t h a t e a c h common f o l l i c u l a r c e l l w o u ld , a t some tim e d u r i n g
i t s a c t i v e s e c r e t o r y p e r i o d , p a s s th r o u g h t h i s t r a n s f o r m a
t i o n . However, t h e r e h a s b e e n no r e s e a r c h c a r r i e d o u t d u r
in g t h i s s tu d y t h a t w ould j u s t i f y such a c o n c l u s i o n .
The t h y r o i d g la n d o f t h e a d u l t h o r s e shows t h e same
g e n e r a l s t r u c t u r e a s t h e 230 mm. embryo, e x c e p t t h a t th e
l a r g e r f o l l i c l e s a r e much more num erous and h a v e g r e a t e r
d im e n s io n s ; and t h a t t h e r e i s a n abundance o f i n t e r f o l l i c u
l a r c e l l s w h ic h c o n t a i n many s m a ll f o l l i c l e s o f v a r y i n g
s h a p e s and s i z e s . A p p a r e n t l y i n t h e a d u l t m ost new f o l l i
c l e s a r i s e , a s n e e d e d , from t h e s e d i f f e r e n t i a t i n g i n t e r
f o l l i c u l a r c e l l s r a t h e r t h a n from b u d d in g f o l l i c l e s , w h ich
51
h ave b e e n foun d o n ly o c c a s i o n a l l y i n t h i s m a t e r i a l . The
l o o s e , s c a t t e r e d , e p i t h e l i a l c e l l s , c h a r a c t e r i s t i c o f th e
t h y r o i d t i s s u e i n a l l embryos from t h e s t a g e w here f o l l i c u l a r
d e v e lo p m e n t b e g a n , a r e s t i l l fo u n d in t h e a d u l t . The f a c t
t h a t no l a r g e c e l l s w i t h s p h e r i c a l n u c l e i and c l e a r c y t o
p lasm hav e b e e n fo u n d i n th e w a l l s o f t h e f o l l i c l e s o f t h i s
s t a g e o f d e v e lo p m e n t s u g g e s t s t h e c o n c l u s i o n t h a t t h e s e
c e l l s may be f u n c t i o n i n g e le m e n ts c h a r a c t e r i z i n g t h a t p e r i o d
o f d e v elo p m e n t when r a p i d body g ro w th and m a t u r i t y a r e
o c c u r r i n g . The c o l l o i d w i t h i n t h e f o l l i c l e s show fe w e r
v a c u o l e s th a n i n t h e 180 mm. and 230 mm. em bryos. A ls o ,
t h e r e i s a ch an ge i n t h e c h e m ic a l n a t u r e o f t h e c o l l o i d a s
e v id e n c e d by i t s d i f f e r e n t c o l o r r e a c t i o n to t h e same t y p e s
o f s t a i n s a s t h o s e u s e d i n s t a i n i n g t h e s e c t i o n s o f t h e em
b r y o n i c t h y r o i d s . T hese f a c t s a l l c o n t r i b u t e e v id e n c e to
th e f a c t t h a t t h e demands made upon t h e t h y r o i d g l a n d i n th e
a d u l t i n d i v i d u a l d i f f e r from t h o s e made upon t h e g la n d d u r
in g p e r i o d s o f body g ro w th and d e v e lo p m e n t.
V I. s m m R Y
T h is i n v e s t i g a t i o n i s b a s e d on t h e h i s t o l o g i c a l s tu d y
o f tw e n ty - o n e h o r s e embryos v a r y i n g from 5 mm. to 21 mm.
crow n-rum p m e a su re m e n t, and o f a s e r i e s o f s e c t i o n s o f an
a d u l t g l a n d .
1 . Most o f th e o b s e r v a t i o n s c o n c e r n in g t h e o r i g i n
and t h e v a r i o u s s t a g e s o f t h e m o rp h o g e n e s is o f t h e t h y r o i d
o f t h e h o r s e co n fo rm v /ith t h o s e r e c o r d e d by N o r r i s f o r t h e
human; h o w e v er, i t i s o b s e rv e d t h a t th e p rim a ry f o l l i c l e s do
n o t d e v e lo p from f e n e s t r a t e d p l a t e s l o n g i t u d i n a l l y a r r a n g e d ,
b u t from t w o - c e l l e d b r a n c h e d c o r d s e x te n d in g i n t o t h e c o n
n e c t i v e t i s s u e i n v a r i o u s d i r e c t i o n s w i t h i n p l a n e s p a r a l
l e l i n g t h e t r a n s v e r s e s e c t i o n s o f t h e g l a n d .
2 . The f o l l i c l e s a r e n o t l i b e r a t e d from t h e c o r d s by
c o n s t r i c t i o n s due to in g ro w th o f m esenchym al t i s s u e , o r by
b e i n g f o r c e d o u t by i n c r e a s e d p r e s s u r e due to t h e i n c r e a s e
o f c e l l s b e tw e e n i n d e n t a t i o n s , b u t t h e e n t i r e c o rd w i t h i t s
f o l l i c l e s p a s s e s t h r o u g h a p r o c e s s o f c o m p le te d i s s o c i a t i o n
o f t h e c e l l s . The s e g r e g a t e d c e l l s a r e t h e n r e o r g a n i z e d i n
to s o l i d m a sse s w h ich l a t e r a c q u i r e a lu m en .
3 . In t h e w a l l s o f f o l l i c l e s c o n t a i n i n g c o l l o i d ,
a p p e a r i n g f o r t h e f i r s t tim e i n t h e 158 mm. em bryo, one to
s e v e r a l c e l l s l a r g e r t h a n t h e common f o l l i c u l a r c e l l s , and
h a v in g c l e a r c y to p la s m and s p h e r i c a l n u c l e i w h ich s t a i n
l i g h t l y , a p p e a r i n t h e w a l l o f t h e f o l l i c l e . They seem to
53
be a s s o c i a t e d w i t h t h e s e c r e t o r y f u n c t i o n .
4 . The a d u l t t h y r o i d g la n d i s c h a r a c t e r i z e d by many
v e r y l a r g e , s p h e r o i d a l f o l l i c l e s w i t h i r r e g u l a r s u r f a c e s and
low c o lu m n ar e p i t h e l i u m ; a n d , by q u a n t i t i e s o f i n t e r f o l l i c
u l a r c e l l s , fo u n d s i n g l y o r i n m asses i n w h ic h num erous
s m a ll f o l l i c l e s a r e d i f f e r e n t i a t i n g . The d i f f e r e n t c h e m ic a l
n a t u r e o f t h e c o l l o i d , and t h e a b s e n c e o f l a r g e c e l l s c o n
t a i n i n g s p h e r i c a l n u c l e i and c l e a r c y to p la s m w i t h i n t h e
f o l l i c u l a r w a l l , s u g g e s t t h a t t h e demands made upon t h e t h y
r o i d o f t h e a d u l t d i f f e r from th o s e made upon t h e t h y r o i d s o f
i n d i v i d u a l s p a s s i n g th r o u g h t h e p e r i o d o f r a p i d body g ro w th
and d e v e lo p m e n t.
VII. BIBLIOGRAPHY
A rx , J o s e f vo n 1928 The t h y r o i d o f t h e h o r s e a t v a r i o u s
a g e s . D i s s e r t a t i o n U n i v e r s i t a t B e rn .
A s c h o f f , L. 19 24a On c e n t r a l f o l l i c l e s . L e c t u r e s on
P a t h o l o g y . P a u l B. E o e h e r , I n c . , New Y ork. 365 pp.
B e n s le y , R. R. 1914 On o v o id c e l l s . A n a t. R e c ., v o l . 8:
4 3 1 -4 4 0 .
B radw ay, W in n if re d 1929 M o rp h o g e n e sis o f t h y r o i d f o l l i c l e s
o f t h e c h i c k . A n a t. R e c ., v o l . 42 (2): 1 5 7 -1 7 6 .
Cowdry, E. V. 1934 A T ex tb o o k o f H i s t o l o g y . L ea and
F e b i g e r , P h i l a d e l p h i a .
Godwin, M e lv in C raw fo rd 1936 The e a r l y d ev elo p m e n t o f t h e
t h y r o i d g l a n d i n t h e dog w i t h e s p e c i a l r e f e r e n c e to th e
o r i g i n and p o s i t i o n o f a c c e s s o r y t h y r o i d t i s s u e w i t h i n
t h e t h o r a c i c c a v i t y . A n a t. R e c ., v o l . 66: 2 3 3 -2 4 6 .
. . . . , 1937 Complex IV in t h e dog w i t h s p e c i a l e m p h a sis
on t h e r e l a t i o n o f t h e u l t i m o b r a n c h i a l body to i n t e r
f o l l i c u l a r c e l l s i n p o s t n a t a l t h y r o i d g l a n d . Am. J .
A n a t . , v o l . 60: 2 9 9 -3 2 9 .
H a r r i s o n , B ru ce M. 1924 A m o d i f i c a t i o n o f r e c o n s t r u c t i o n
m e th o d s. S c i e n c e , v o l . 50: 1 6 1 -1 6 2 .
H i l l , B. H. 1935 The e a r l y d e v e lo p m e n t o f t h y r o i d g l a n d
i n Amia c a l v a . J o u r . M o r p h ., v o l . 57 (2 ) : 5 3 3 -5 4 5 .
H o p k in s, M a rie L . 1935 D evelopm ent o f t h y r o i d g la n d in
c h i c k em bryo. J o u r . M o rp h ., v o l . 52 (2 ): 5 8 5 -6 1 1 .
J a c k s o n , J . L . 1931 The sh ap e and s i z e o f th e human t h y
r o i d f o l l i c l e i n h e a l t h and d i s e a s e . A n a t. R ec., v o l .
48: 2 1 9 -2 3 9 .
J o n e s , C. H. 1836 T h y ro id g l a n d . T odd ’ s C y c lo p e d ia o f
Anatomy and P h y s i o l o g y , v o l . 4 , p p . 1 1 0 2 -1 1 1 8 .
K e ib a l and M all 19 1 0 -1 2 Manual o f Human E m bryology.
J . B. L i p p i n c o t t Co., P h i l a d e l p h i a , v o l . 1 and 2.
K in g s b u r y , B. F . 1 935a On t h e f a t e o f t h e u l t i m o b r a n c h i a l
body w i t h i n human t h y r o i d g l a n d . A n a t. R e c ., v o l . 61
( 2 ) : 1 5 5 -1 7 3 .
55
M a rin e , D. 1932 Cow dry’ s S p e c ia l C y to lo g y , I I . p p . 7 9 9 -8 5 5 .
P a u l P . H o e b e r, I n c . , New Y ork.
Maximow, A. A. and Bloom, W. 1934 A T ex tb o o k o f H i s t o l o g y .
W. B. S a u n d e rs Co., P h i l a d e l p h i a .
N o n id e z , J . F. 193 2a P a r a f o l l i c u l a r c e l l s . Am. J . A n a t . ,
v o l . 49: 4 7 9 -5 0 5 .
. . . . , 1932b A n a t. R e c ., v o l . 53: 3 5 3 .
N o r r i s , E. H. 1916 The m o rp h o g e n e sis o f t h e f o l l i c l e s in
t h e human t h y r o i d g l a n d . Am. J . A n a t . , v o l . 20: 411-
448.
. . . . , 1918 The e a r l y m o rp h o g e n e sis o f t h e human t h y
r o i d g l a n d . I b i d . , v o l . 24: 4 4 3 -4 6 5 .
Raymond, N. 1932 P a r a f o l l i c u l a r c e l l s o f t h e t h y r o i d o f th e
r a b b i t . A n a t. R e c ., v o l . 53: 5 5 5 -5 6 5 .
R e i n h o f f , V/. F. , J r . 1929 G ro s s and m ic r o s c o p ic s t r u c t u r e
o f t h e t h y r o i d g l a n d i n man. A rc h . S u rg . , v o l . 19 ( 6 ) :
1 9 8 6 -1 0 3 6 .
R e i s i n g e r , Ludwig 1928 D ie S c h i l d d r u s e d e s P f e r d e s . Z o o l.
A n z ., v o l . 79: 6 5 -6 8 .
S a n d e r s , J a s . M. 1935 The d e v e lo p m e n t o f t h e t h y r o i d g la n d
i n U r o d e le s . J o u r . M o rp h ., v o l . 57 (2 ): 5 9 7 -6 1 5 .
S e e c o f f , D. P . 1927 M i t o c h o n d r i a - r i c h c e l l s . Am. J . P a t h . ,
v o l . 3: 3 6 5 -3 8 4 .
S i s s o n , S e p tim u s 1927 The anatom y o f t h e d o m e s tic a n im a l s .
W. B. S a u n d e rs , P h i l a d e l p h i a and London.
V /e lle r, G. L o u i s , J r . 1933 D evelopm ent o f t h y r o i d , p a r a
t h y r o i d and thym us in Man. C a rn e g ie I n s t . Wash.
( P u b l . 4 4 3 ) . C o n t r . to Emb. , v o l . 24: 9 5 -1 3 8 .
W illia m s o n , G. S. and P e a r s e , J . H. 1923 The s t r u c t u r e o f
t h e t h y r o i d g la n d i n man. J . P a t h , and B a c t . , v o l . 26:
459.
W ils o n , G. E. 19 27-28 The t h y r o i d f o l l i c l e i n man: i t s
n o rm al and p a t h o l o g i c a l c o n f i g u r a t i o n . A n a t. R e c .,
v o l . 37: 3 1 -6 1 .
56
Z e c h e l , G. 1931 F o l l i c u l a r d e s t r u c t i o n i n t h e n o rm al t h y
r o i d o f t h e d o g . S u r g . , G y n e c o l. , and Obs t . , v o l . 52:
2 2 8 -2 3 2 .
. . . . , 1932 C e l l u l a r s t u d i e s on t h e t h y r o i d g l a n d . S u rg .
G y n e c o l., and O b s t . , v o l . 54: 1 - 5 .
. . . . , 1933 O b s e r v a t i o n s on t h e f o l l i c u l a r c y c l e and on
t h e p r e s e n c e o f t h e m a c r o th y r o c y te i n t h e human t h y
r o i d . A n a t. R e c ., v o l . 56: 1 1 9 -1 3 0 .

Asset Metadata

Creator Brooks, Eva (author)

Core Title The progressive histological differentiation of the thyroid gland of the horse

Contributor Digitized by ProQuest (provenance)

Degree Master of Science

Publisher University of Southern California (original), University of Southern California. Libraries (digital)

Tag Biological Sciences,OAI-PMH Harvest

Format application/pdf (imt)

Language English

Permanent Link (DOI) https://doi.org/10.25549/usctheses-c39-254060

Unique identifier UC11315071

Identifier EP67098.pdf (filename),usctheses-c39-254060 (legacy record id)

Legacy Identifier EP67098.pdf

Dmrecord 254060

Document Type Thesis

Format application/pdf (imt)

Rights Brooks, Eva

Type texts

Source University of Southern California (contributing entity), University of Southern California Dissertations and Theses (collection)

Access Conditions The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the au...

Repository Name University of Southern California Digital Library

Repository Location USC Digital Library, University of Southern California, University Park Campus, Los Angeles, California 90089, USA

Linked assets

University of Southern California Dissertations and Theses