Craniofacial skeleton development requires the patterning of skeletogenic neural crest (NC) cells along the dorsal-ventral (DV) axis. NC cells populate structures know as the pharyngeal arches and are surrounded by layers of ectoderm and endoderm. The nested expression of patterning genes divides NC cells into three distinct DV domains, dorsal, intermediate, and ventral, which correspond to later cartilage morphology. Bmp and Wnt signaling pathways are both implicated to be required for pharyngeal arch patterning but the mechanisms regulating this are largely unknown. In my thesis I examine the roles of Bmp and Wnt signaling in pharyngeal arch DV patterning using zebrafish as a model organism.
Transgenic reporter zebrafish lines show that NC cells are responsive to Bmp and Wnt signaling arising from the overlying pharyngeal ectoderm. To examine the functional roles of Wnt and Bmp signaling in NC cells I utilize a loss of function approach with temporally regulated transgenic heat shock lines. The use of conditional heat shock lines allows us to bypass early signaling requirements and determine the stage specific requirements for Bmp and Wnt signaling in DV patterning. Loss of Bmp signaling results in the reduction of ventral-intermediate elements and disruption of DV patterning genes such as hand2, jag1b, dlx5/6, and dlx3. This closely resembles an endothelin-1 (Edn1) loss of function phenotype. Rescue experiments reveal that Bmp and Edn1 signaling have distinct spatiotemporal DV patterning requirements. In early arch development Bmp is upstream of Edn1 in ventral patterning while in later arch development Bmp and Edn1 have independent roles; Bmps specify the ventral domain and Edn1 the intermediate domain. A loss of Wnt function phenotype also shows reduction of ventral-intermediate structures and patterning genes, closely resembling a Bmp and Edn1 loss of function phenotype. Preliminary evidence suggests that Wnt signaling is required for the competency of NC cells to respond to Bmp signaling and may be an upstream regulator of Edn1 expression. In my thesis I therefore show that ectoderm derived Edn1, Bmp, and Wnt signaling cues are required for DV patterning of the pharyngeal arches.
|Advisor:||Schilling, Thomas F.|
|Commitee:||Arora, Kavita, Cho, Ken, Monuki, Edwin S., Steele, Robert E.|
|School:||University of California, Irvine|
|Department:||Biological Sciences - Ph.D.|
|School Location:||United States -- California|
|Source:||DAI-B 74/05(E), Dissertation Abstracts International|
|Subjects:||Genetics, Developmental biology|
|Keywords:||Bmp, Craniofacial skeleton, Dorsal-ventral patterning, Edn1, Neural crest, Pharyngeal arch, Signaling regulation, Wnt, Zebrafish|
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