Regulation of Neural Crest Cell Fate by Foxd3

描述（由申请人提供）：神经嵴在发育早期出现，由同质细胞群组成，产生各种细胞类型，包括色素细胞、软骨细胞和周围神经系统的神经元。众所周知，这一特定过程以及由此产生的细胞系的存活依赖于环境线索和转录网络的精确调节，但许多分子机制仍不清楚。我们建议研究转录抑制因子foxd3在神经嵴规范和神经嵴衍生黑素细胞谱系的后续维持中的作用。作为斑马鱼神经嵴三种色素细胞之一，Mitfa的表达对黑色素细胞的形成是必要和充分的。我们假设foxd3调节mitfa表达，并与c-kit信号通路相互作用，以控制神经嵴的规范和黑素细胞谱系的维持。阐明mitfa和黑色素细胞分化的调控可能为色素细胞疾病（如神经纤维瘤病和黑色素瘤）的机制提供洞见。

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.