HUMAN GENETICS
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DETERMINING THE ROLE OF GROWTH DIFFERENTIATION FACTOR-6 (GDF6) IN THE DEVELOPMENT OF THE CORONAL SUTURE
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DAWN ELIZABETH CLENDENNING
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Dissertation under the direction of Professor Douglas P. Mortlock
<p> Growth differentiation factor-6 (Gdf6) is a member of the Bone Morphogenetic Protein (BMP) family of secreted signaling proteins. The Gdf6 mutant mouse presents with fusions in the bones of the wrist and ankle, hypoplasia of the thyroid cartilage, abnormalities of the bones of the middle ear, and craniosynostosis of the coronal suture. Craniosynostosis is the premature fusion of one or more of the cranial sutures, the joints that separate the flat bones of the skull.
<p> The primary objective of this work was to determine the developmental timing of the coronal suture defect, when and where Gdf6 is expressed during cranial development, what mechanism leads to fusion of the coronal suture, and how Gdf6 interacts with other members of the BMP family in coronal suture development. We found that Gdf6 is expressed in the rudiment of the frontal bone early in suture development. Loss of Gdf6 leads to the osteogenic differentiation of the coronal suture mesenchyme, which must remain undifferentiated to remain a site for cranial growth. Furthermore, Gdf6 interacts with fellow BMP family member Bmp4 not only in the development of the coronal suture, but in multiple skeletal elements. Additionally, we found that the BMP antagonist Noggin does not play an important role in embryonic suture development. The findings of this project not only further the the study of craniosynostosis but also broadens the knowledge of the roles of BMPs.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-04162012-160010 |
| Date | 26 April 2012 |
| Creators | Clendenning, Dawn Elizabeth |
| Contributors | Douglas P. Mortlock, Patricia Labosky, Xiangli Yang, Michelle Southard-Smith, Ela W. Knapik |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-04162012-160010/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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