Placode lineage contribution to Hirschsprung's disease

描述（由申请人提供）：巨结肠病是一种先天性肠道运动障碍，由神经嵴无法迁移到胃肠道引起。神经cres负责肠神经系统的形成，它们的缺失导致末端肠的神经节段，这导致不能促进蠕动收缩。本提案中描述的新观察结果导致了一个模型，在这个模型中，基板细胞也会迁移并定植在肠道中，并选择性地产生肠道的内在感觉神经元

DESCRIPTION (provided by applicant): Hirschsprung's disease is a congenital gut motility disorder caused by the failure of neural crest migration to the gastrointestinal tract. Neural cres is responsible for formation of the enteric nervous system, and their absence results in an aganglionic segment in the terminal bowel, which results in a failure to promote peristaltic contraction. New observations described in this proposal lead to a model in which placode cells also migrate and colonize the gut and selectively give rise to the intrinsic sensory neurons of the enteric ganglia, whereas neural crest cells contribute to non-sensory population (motor neurons, interneurons, and glia). In this application, I propose experiments to define the fate of enteric placode in the enteric nervous system, and to address how endothelin and Ret signaling control both neural crest and placode cell migration and colonization of the gut. Furthermore, I propose to address a model in which the intrinsic airway ganglia of the pulmonary plexus are also derived from both placode and neural crest, which will provide new insight into pathogenesis of the Hirschsprung's disease associated syndrome, Congenital central hypoventilation syndrome (CCHS).