Regulation of Neural Crest Cell Fate by Foxd3

描述(申请人提供)：神经脊出现在发育的早期，由同质的细胞群组成，这些细胞可以产生各种类型的细胞，包括色素细胞、软骨和周围神经系统的神经元。众所周知，这种指定过程以及由此产生的细胞谱系的生存依赖于环境线索和转录网络的精确调控，但许多分子机制仍不清楚。我们建议研究转录抑制因子foxd3在神经峰的指定和随后神经峰来源的黑素细胞谱系的维持中的作用。Mitfa的表达对于黑素细胞的特性是必要和充分的，黑素细胞是来源于斑马鱼Danio rerio神经脊的三种类型的色素细胞之一。我们假设foxd3调节mitfa的表达，并与c-kit信号通路相互作用，以控制神经峰的指定和黑素细胞谱系的维持。阐明丝裂原和黑素细胞分化的调节可能有助于深入了解色素细胞疾病的机制，如神经纤维瘤病和黑色素瘤。

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.