Requirements for Wnt signaling in morphogenesis of the neural crest, neural tube, and craniofacial skeleton of zebrafish embryos

How are morphogenesis, growth, and differentiation orchestrated to generate multiple functioning organs during embryonic development? For my thesis studies I have focused on understanding the role of Wnt signaling in several organs and cell types during zebrafish embryonic development. I studied context-specific requirements for Wnt signals to pattern the neural crest (NC)-derived pigment cells and craniofacial skeleton. Additionally, I studied the roles of Ovo transcription factors, putative Wnt targets, in the formation of the central nervous system (CNS).;The CNS rudiment, the neural tube, forms by the rolling into a tube of the neuroectoderm during neurulation. NC cells form adjacent to the neuroectoderm but migrate throughout the embryo to differentiate into a variety of cell types including cartilage cells that give rise to the craniofacial skeleton and pigment cells of the skin. Differential Cadherin expression differentiates the neural tube from NC during neurulation. Additionally, a sequential Cadherin code, partially controlled by Wnt signaling, is also required for NC cell migration.;Wnt signaling is well known in embryogenesis and cancer, playing multiple roles in several aspects of development. I have isolated and characterized requirements in neural tube morphogenesis for two zebrafish orthologues of the Ovo family of transcription factors, ovo1 and ovo3. I also established zebrafish ovo1 as a target of Wnt signaling required for the migration of the NC-derived pigment cells and provided the first link between Ovo transcription factors and N-cadherin (Ncad) regulation via transcriptional control of Rab Gtpases known to control trafficking of molecules within the cell.;Wnt signaling also functions to pattern the NC-derived craniofacial skeleton. Using temporally controlled gain-of-function studies I have shown that Wnt signaling is required for the formation of the lower jaw skeleton by coordinating morphogenesis and growth. My research shows that Dkk1 overexpression inhibits Wnt signaling, which is sufficient to inhibit cell proliferation resulting in craniofacial abnormalities. Although expressed by the adjacent endoderm, Dkk1 acts as an extrinsic cue to organize growth and morphogenesis of the craniofacial skeleton.