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NON-CANONICAL TGF-BETA SIGNALING PATHWAY
IN CRANIOFACIAL DEVELOPMENT
by
Jieun Kim
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(CRANIOFACIAL BIOLOGY)
May 2009
Copyright 2009 Jieun Kim
Object Description
| Title | Non-canonical Tgf-beta signaling in craniofacial development |
| Author | Kim, Ji Eun |
| Author email | jiek@usc.edu; jieunbucks@gmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Cranio-Facial Biology |
| School | School of Dentistry |
| Date defended/completed | 2009-03-11 |
| Date submitted | 2009 |
| Restricted until | Unrestricted |
| Date published | 2009-04-28 |
| Advisor (committee chair) | Kaartinen, Vesa |
| Advisor (committee member) |
Snead, Malcolm Chai, Yang Shi, Wei Bellusci, Saverio |
| Abstract | Craniofacial malformations including cleft lip, cleft palate and craniosynostosis are among the most common birth defects in humans. A Tgf-β signaling pathway has been shown to be important during craniofacial development. Detailed mechanisms of the canonical Tgf-β signaling pathway in vitro have been well established, and a significant amount of information has been accumulated about a role of the canonical Tgf-β signaling pathway in craniofacial development. However, the canonical Tgf-β signaling pathway alone is not enough to explain all of the published findings of different craniofacial phenotypes in mice harboring mutations in genes encoding Tgf-β signal transduction components in vivo. Therefore, we hypothesized that a non-canonical Tgf-β signaling pathway also acts as an essential player in craniofacial development. To this end, we studied a function of the non-canonical Tgf-β signaling pathway in craniofacial development using three different approaches. First, we discovered that non-conventional Tgf-β receptor combinations can also act as functional receptor complexes. Second, we studied a role of Rac1, as a possible downstream mediator of Tgf-βs, in craniofacial development using the tissue-specific knockout mouse model system. We found out that Rac1 is an essential factor in the craniofacial development, and an important regulator of neural crest cell behavior. Third, to find out a function of Trim33, which was recently identified as a Smad4-independent regulator of Tgf-β signaling, we generated the Trim33 conditional knockout mouse line. We discovered that Trim33 is required for the early embryonic development. This study shows that the non-canonical Tgf-β signaling pathway is also essential factor in craniofacial development. |
| Keyword | Tgf-beta; craniofacial biology; Rac1; Trim33; conditional knockout mouse |
| 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-m2133 |
| Rights | Kim, Ji Eun |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Kim-2780 |
| Archival file | uscthesesreloadpub_Volume26/etd-Kim-2780.pdf |
Description
| Title | Page 1 |
| Full text | NON-CANONICAL TGF-BETA SIGNALING PATHWAY IN CRANIOFACIAL DEVELOPMENT by Jieun Kim A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (CRANIOFACIAL BIOLOGY) May 2009 Copyright 2009 Jieun Kim |
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