Patterning and Stabilizing the Zebrafish Pharyngeal Arch Intermediate Domain

Talbot, Jared Coffin, 1982-

Patterning and Stabilizing the Zebrafish Pharyngeal Arch Intermediate Domain

dc.contributor.author	Talbot, Jared Coffin, 1982-
dc.date.accessioned	2012-02-29T21:24:21Z
dc.date.available	2012-02-29T21:24:21Z
dc.date.issued	2011-09
dc.description	xv, 76 p. : ill. (some col.) Includes 4 video files.	en_US
dc.description.abstract	Improved understanding of pharyngeal arch (PA) patterning and morphogenesis can reveal critical insights into the origins of craniofacial diseases, such as Fraser syndrome. PAs contain mesenchymal condensations, which give rise to most of the facial skeleton in vertebrates. Studies of Endothelin1 signaling reveal that the skeleton derived from the first two PAs are patterned into dorsal, intermediate, and ventral domains. Previous work has indicated that endothelin targets, including the Dlx genes, homeotically pattern dorsal versus ventral PA identity. I show that the Dlx gene family plays a vital role in PA intermediate-domain identity establishment. In WT fish, the PA intermediate domain is delineated by combined expression of all Dlx genes. Reduction of Dlx gene function results in loss of intermediate-domain identity. Conversely, ventral expansion of Dlx expression, seen in hand2 mutants, results in ventral expansion of intermediate-domain identity. Hence, PA intermediate-domain identity is defined by co-expression of Dlx genes. Epithelial-mesenchymal interactions play an important part in PA intermediate-domain morphogenesis. Zebrafish fras1 (epithelially expressed) and itga8 (mesenchymally expressed) mutants also show specific defects within intermediate-domain skeleton and epithelia. Facial phenotypes in fras1;itga8 double mutants look extremely similar to either single mutant, suggesting that fras1 and itga8 might participate in the same epithelial-mesenchymal interaction during PA intermediate-domain formation. Our developmental studies reveal that fras1 - and itga8 -dependent epithelial segmentation of the PA intermediate domain stabilizes developing skeletal elements. Lesions in human FRAS1 underlie many cases of Fraser syndrome, and this work provides an excellent developmental model for the craniofacial defects found in Fraser syndrome. Loss of either Dlx or fras1 function produces defects in the PA intermediate domain, yet seemingly during different developmental periods. Nonetheless, combined reduction of both Dlx and fras1 function synergistically increases skeletal defects, implying a molecular connection between early (Dlx -mediated) pattern formation and later (fras1 -mediated) pattern stabilization. Elucidation of the Dlx-fras1 interaction is an interesting topic which may unveil new molecules pertinent to Fraser syndrome. Supplemental movies highlighting skeletal and epithelial morphogenesis accompany this dissertation.	en_US
dc.description.sponsorship	Committee in charge: Judith S. Eisen, Chairperson; Charles B. Kimmel, Advisor; John H. Postlethwait, Member; Chris Q. Doe, Member; Kennith E. Prehoda, Outside Member	en_US
dc.identifier.uri	https://hdl.handle.net/1794/11982
dc.language.iso	en_US	en_US
dc.publisher	University of Oregon	en_US
dc.relation.ispartofseries	University of Oregon theses, Dept. of Biology, Ph. D., 2011;
dc.rights	rights_reserved	en_US
dc.subject	Genetics	en_US
dc.subject	Evolution and development	en_US
dc.subject	Biological sciences	en_US
dc.subject	Craniofacial	en_US
dc.subject	Dlx	en_US
dc.subject	Fras1	en_US
dc.subject	Hand2	en_US
dc.subject	Itga8	en_US
dc.subject	Skeleton	en_US
dc.subject	Zebrafish	en_US
dc.subject	Pharyngeal arch	en_US
dc.subject	Intermediate domain	en_US
dc.subject	Developmental biology	en_US
dc.title	Patterning and Stabilizing the Zebrafish Pharyngeal Arch Intermediate Domain	en_US
dc.type	Thesis	en_US