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INTEGRIN EXPRESSION AND SIGNALING DURING PALATAL FUSION by Daniela Schmid 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) August 2008
Copyright 2008
Daniela Schmid
Object Description
| Title | Integrin expression and signaling during palatal fusion |
| Author | Schmid, Daniela |
| Author email | dschmid@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Cranio-Facial Biology |
| School | School of Dentistry |
| Date defended/completed | 2008-06-10 |
| Date submitted | 2008 |
| Restricted until | Unrestricted |
| Date published | 2008-07-29 |
| Advisor (committee chair) | Shuler, Charles |
| Advisor (committee member) |
Lee, Matthew Chai, Yang Paine, Michael Frenkel, Baruch |
| Abstract | The fusion of the secondary palate is a complex event requiring epithelial and mesenchymal cell differentiation. Palatal fusion and mesenchymal confluence entail adhesion of the opposing medial edge epithelia (MEE), extracellular matrix (ECM) remodeling and MEE disappearance. In this process the MEE are believed to undergo epithelial-mesenchymal transformation (EMT). While E-cadherin mediates cell-cell adhesion, integrins are the major cell surface receptors. Integrins transduce ECM signals into the cell by associating with adaptor proteins such as integrin-linked kinase (ILK). Integrin and growth factor receptor signaling has been implicated in the regulation of EMT. We hypothesized that integrin signaling is necessary for palatal fusion. To assess this, we examined E-cadherin, beta1 integrin and ILK expression. Immunohistochemistry demonstrated that E-cadherin expression was downregulated in the MEE prior to EMT. During palatal fusion, beta1 integrin strongly immunolocalized to the MEE and oral epithelia while ILK expression was restricted to the MEE. Silencing of either beta1 integrin or ILK by siRNA transfection into palate organ culture resulted in the persistence of MEE cells in the midline. Western blot confirmed the protein reduction. Finally, epidermal growth factor-induced ILK signaling was assessed in palate cultures treated with either ILK siRNA or non-silencing control siRNA.; The resulting phosphorylation of the known ILK downstream mediators GSK-3beta and Akt was then assessed. ILK silencing significantly reduced the phosphorylation of both proteins. These results suggest that palatal fusion and the onset of mesenchymal transdifferentiation of the MEE is correlated with the downregulation of E-cadherin, beta1 integrin and integrin-linked kinase. Integrin signaling through integrin-linked kinase and its downstream partners GSK-3beta and Akt is crucial for EMT as reduction of beta1 integrin and integrin-linked kinase expression prevented palatal fusion resulting in a cleft palate. |
| Keyword | palate development; integrin-linked kinase; beta1 integrin |
| 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 |
| Type | texts |
| Legacy record ID | usctheses-m1438 |
| Rights | Schmid, Daniela |
| 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-Schmid-20080729 |
| Archival file | uscthesesreloadpub_Volume23/etd-Schmid-20080729.pdf |
Description
| Title | Page 1 |
| Full text | INTEGRIN EXPRESSION AND SIGNALING DURING PALATAL FUSION by Daniela Schmid 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) August 2008 Copyright 2008 Daniela Schmid |
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