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JAGGED1 FUNCTIONS DOWNSTREAM OF TWIST1 IN THE SPECIFICATION OF
THE CORONAL SUTURE AND THE FORMATION OF A BOUNDARY BETWEEN
OSTEOGENIC AND NON-OSTEOGENIC CELLS
by
Hai-Yun Yen
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
(BIOCHEMISTRY AND MOLECULAR BIOLOGY)
December 2009
Copyright 2009 Hai-Yun Yen
Object Description
| Title | Jagged1 functions downstream of Twist1 in the specification of the coronal suture and the formation of a boundary between osteogenic and non-osteogenic cells |
| Author | Yen, Hai-Yun |
| Author email | hyen@usc.edu; haiyunyen@yahoo.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Biochemistry & Molecular Biology |
| School | Keck School of Medicine |
| Date defended/completed | 2009-10-27 |
| Date submitted | 2009 |
| Restricted until | Restricted until 20 Nov. 2010. |
| Date published | 2010-11-20 |
| Advisor (committee chair) | Maxson, Robert E. |
| Advisor (committee member) |
Dubeau, Louis Roy-Burman, Pradip Crump, Gage |
| Abstract | In this dissertation, I would like to address how the evolutionarily conserved Notch signaling molecules regulate the formations of murine cranial bones and sutures. Mutations in the Notch ligand, JAGGED1, cause Alagille syndrome, which has craniosynostosis as a feature. The expression pattern of Jagged1 at mouse coronal suture suggested that it might play a role in establishing boundary between osteogenic and non-osteogenic cells. Tissue-specific knockout of Jagged1 in mouse mesoderm affected the expression of downstream Notch signaling at sutural cells and resulted in craniosynostosis. Immunostaining results also implied that the boundary between presumptive cranial bones has been established by Notch signaling at early stage, while the opposing osteogenic fronts of the bones are still far away from each other. I further demonstrated the genetic interactions between Notch signaling and Twist1 which is animportant pathogenic gene in regulating cranial sutures morphogenesis. Twist1 regulates Notch signaling in sutural mesenchyme and maintain suture patency. The phenotypic studies of mouse skulls and middle ear ossicles indicated that Jagged1 interacts functionally with Twist1 in several distinct developmental settings. This work reveals a molecular network that controls cranial development, and establishes a new model of boundary formation at developing cranial suture. |
| Keyword | Jagged1; Twist1; cranial suture; boundary formation |
| 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-m2750 |
| Contributing entity | University of Southern California |
| Rights | Yen, Hai-Yun |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | cisadmin@lib.usc.edu |
| Filename | etd-YEN-3384 |
| Archival file | uscthesesreloadpub_Volume56/etd-YEN-3384.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@lib.usc.edu |
| Full text | JAGGED1 FUNCTIONS DOWNSTREAM OF TWIST1 IN THE SPECIFICATION OF THE CORONAL SUTURE AND THE FORMATION OF A BOUNDARY BETWEEN OSTEOGENIC AND NON-OSTEOGENIC CELLS by Hai-Yun Yen 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 (BIOCHEMISTRY AND MOLECULAR BIOLOGY) December 2009 Copyright 2009 Hai-Yun Yen |
