Functional analysis of early vagal neural crest and ENS development

描述（由申请人提供）：肠神经系统（ENS）是周围神经系统中最复杂和最大的部分。ENS由一系列复杂的相互连接的神经元和神经胶质组成，它们控制肠道运动并调节肠壁内的血液流动。在发育过程中，ENS起源于迷走神经嵴细胞，这些细胞从尾侧后脑水平的神经管迁移而来。在到达前肠后，迷走神经来源的肠神经嵴细胞沿着发育中的肠尾端迁移并分化为

DESCRIPTION (provided by applicant): The enteric nervous system (ENS) is the most complex and largest portion of the peripheral nervous system. The ENS is comprised of a complex series of interconnected neurons and glia that control intestinal motility and regulate blood flow within the gut wall. During development, ENS arises from vagal neural crest cells that emigrate from the neural tube at caudal hindbrain levels. Upon reaching the foregut, the vagal-derived enteric neural crest cells migrate caudally along the developing gut and differentiate into enteric neurons and glial cell types. Abnormalities in migration to or along the gut or along resul in birth anomalies like Hirschsprung's Disease, in which the distal portion of the intestine is devoid of enteric neurons or glia, resulting in megacolon and chronic constipation. While much research attention has focused on the functional analysis of enteric neural crest cell migration in the gut during later phases of ENS development, the molecular mechanisms that regulate their migration and the designation of early vagal and enteric neural crest cell identity is poorly understood. The experiments in this proposal will utilize zebrafish and chicken embryos in order to enhance our understanding of the mechanisms that regulate early phases of vagal neural crest and ENS development. Both chicken and zebrafish embryos develop externally, allowing for easy experimental manipulation and observation. Furthermore, zebrafish embryos are transparent during development allowing for high-resolution analysis of neural crest cell migration. The specific aims are to 1. Investigate the role of Meis3 in development of the zebrafish enteric neural crest, and 2. Elucidate the role and regulation of Hoxb5 in vagal and enteric neural crest development. The results of these experiments will significantly improve our basic understanding of enteric neural crest cell migration and fate specification, thus providing a solid foundation on which to base upstream translational research endeavors.