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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HD047108-02
Application #
7035382
Study Section
Special Emphasis Panel (ZRG1-F03A (20))
Program Officer
Henken, Deborah B
Project Start
2005-03-16
Project End
2008-03-15
Budget Start
2006-03-16
Budget End
2007-03-15
Support Year
2
Fiscal Year
2006
Total Cost
$50,428
Indirect Cost
Name
University of Washington
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Cooper, Cynthia D; Raible, David W (2009) Mechanisms for reaching the differentiated state: Insights from neural crest-derived melanocytes. Semin Cell Dev Biol 20:105-10
Cooper, Cynthia D; Linbo, Tor H; Raible, David W (2009) Kit and foxd3 genetically interact to regulate melanophore survival in zebrafish. Dev Dyn 238:875-86