Regulation of Neural Crest Cell Fate by Foxd3

Foxd3 对神经嵴细胞命运的调节

• 批准号: 6938890
• 负责人: Cynthia D COOPER
• 金额: $ 4.83万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-16 至 2008-03-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6938890
• 关键词: biological signal transduction; cell differentiation; cell growth regulation; gene expression; gene induction /repression; genetic regulation; intermolecular interaction; melanocyte; neural crest; pigments; postdoctoral investigator; protooncogene; transcription factor; zebrafish

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.

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，可产生多种细胞类型，包括周围神经系统的色素细胞、软骨和神经元。已知这种特化过程以及所得细胞谱系的存活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foxd 3在神经嵴特异性和神经嵴衍生黑素细胞谱系的后续维持中的作用。Mitfa的表达是必要的和足够的黑色素细胞，来自斑马鱼神经嵴的三种类型的色素细胞之一的规格。我们假设foxd 3调节mitfa表达并与c-kit信号通路相互作用以控制神经嵴特化和黑素细胞谱系的维持。阐明mitfa和黑色素细胞分化的调节可能提供深入了解色素细胞疾病，如神经纤维瘤病和黑色素瘤的机制。