Regulation of Neural Crest Cell Fate by Foxd3

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DESCRIPTION (provided by applicant): Arising early during development, the neural crest consists of a homogenous population of cells that give rise to a variety of cell types, including pigment cells, cartilage and neurons of the peripheral nervous system. It is known this specification process, as well as survival of the resulting cell lineages, rely on precise regulation of environmental cues and transcriptional networks, yet many of the molecular mechanisms remain unclear. We propose to examine the role of the transcriptional repressor, foxd3, in neural crest specification and subsequent maintenance of the neural crest derived melanocyte lineage. Mitfa expression is necessary and sufficient for the specification of melanophores, one of three types of pigment cells derived from zebrafish Danio rerio neural crest. We hypothesize that foxd3 regulates mitfa expression and interacts with the c-kit signaling pathway to control neural crest specification and maintenance of the melanophore lineage. Elucidating the regulation of mitfa and melanophore differentiation may provide insight into mechanisms underlying pigment cell disorders such as neurofibromatosis and melanoma.