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THE TEMPORAL AND TISSUE SPECIFIC REQUIREMENT OF MSX GENES IN
MURINE SKULL VAULT OSTEOGENESIS
by
Christopher A. Schafer
___________________________________________________________
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(GENETIC, MOLECULAR, AND CELLULAR BIOLOGY)
August 2011
Copyright 2011 Christopher A. Schafer
Object Description
| Title | The temporal and tissue specific requirement of Msx genes in murine skull vault osteogenesis |
| Author | Schafer, Christopher A. |
| Author email | cschafer@usc.edu;caschafer1@gmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Genetic, Molecular and Cellular Biology |
| School | Keck School of Medicine |
| Date defended/completed | 2011-06-17 |
| Date submitted | 2011-07-21 |
| Date approved | 2011-07-22 |
| Restricted until | 2011-07-22 |
| Date published | 2011-07-22 |
| Advisor (committee chair) | Maxson, Robert |
| Advisor (committee member) |
Chai, Yang Dubeau, Louis |
| Abstract | The homeobox genes Msx1 and Msx2 are set of transcription factors known to have both widespread and overlapping expression patterns throughout the developing murine embryo. Conventional inactivation of either or both of these genes has been associated with a variety of congenital abnormalities including defects in calvarial osteogenesis, palate formation, cardiac development, and embryonic lethality. Here we utilize conditional and temporal gene inactivation to investigate the role of these genes in the development of the murine skull vault. ❧ Temporal inactivation of Msx2 revealed a window of requirement for cranial osteogenesis. Concerted loss of both Msx1 and Msx2 showed an unexpected ability of neural crest derived tissues to contribute to the formation of ectopic bone. Along with this we demonstrated a more extended requirement for the basic helix-loop-helix transcription factor, Twist1, which when mutated causes multiple cranial malformations including craniosynostosis. Although conditional inactivation of Msx1 and Msx2 in neural crest or mesoderm derived tissue did manifest deficient frontal and parietal bone development respectively, only mesodermal inactivation resulted in premature coronal suture fusion. However, conditional targeting of Msx1 and Msx2 using either neural crest or mesoderm driven cre recombinase illustrated phenotypes in adjacent calvarial tissues. Consistent with the view that Msx1 and Msx2 are required for specific tissue-tissue interactions in vertebrate development, here I show that these genes act upstream of BMP4 in cranial mesoderm to initiate and maintain osteogenesis in both the parietal and posterior frontal bone regions. Together my data suggest (1) that Msx1, Msx2, and Twist1 have a crucial window of requirement in the formation of the murine skull vault, (2) that mesoderm derived Msx1 and Msx2 function upstream of the morphogen BMP4 to influence posterior frontal bone osteogenesis, (3) that mesoderm derived Msx1 and Msx2 establish and maintain non-osteogenic coronal suture mesenchyme. |
| Keyword | skull vault; neural crest; mesoderm; tamoxifen |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m |
| Rights | Schafer, Christopher A. |
| 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 author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@usc.edu |
| Archival file | uscthesesreloadpub_Volume71/etd-SchaferChr-149.pdf |
Description
| Title | Page 1 |
| Full text | THE TEMPORAL AND TISSUE SPECIFIC REQUIREMENT OF MSX GENES IN MURINE SKULL VAULT OSTEOGENESIS by Christopher A. Schafer ___________________________________________________________ A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (GENETIC, MOLECULAR, AND CELLULAR BIOLOGY) August 2011 Copyright 2011 Christopher A. Schafer |
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