Placode lineage contribution to Hirschsprung's disease

基板谱系对先天性巨结肠的贡献

• 批准号: 9291508
• 负责人: Takako Makita
• 金额: $ 35.44万
• 依托单位: CHILDREN'S HOSPITAL OF LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9291508
• 关键词: Address; Afferent Neurons; Cells; Colon; Congenital Megacolon; Defect; Derivation procedure; Development; Embryo; Endothelin; Enteral; Enteric Nervous System; Etiology; Failure; Ganglia; Gastrointestinal tract structure; Genes; Genetic; In Vitro; Interneurons; Intestines; Lead; Ligands; Logic; Lung; Modeling; Motor Neurons; Movement; Mus; Mutation; Names; Nerve; Nervous system structure; Neural Crest; Neural Crest Cell; Neuroglia; Neurons; Pathogenesis; Pathology; Peripheral Nervous System; Population; Process; Reagent; Respiratory System; Respiratory tract structure; Role; Sensory; Signal Transduction; Source; Syndrome; Systems Development; base; cell motility; cellular targeting; congenital central hypoventilation syndrome; defined contribution; experimental study; imaging approach; in vivo; insight; migration; motility disorder; nerve stem cell; nervous system disorder; novel; progenitor; public health relevance; receptor; relating to nervous system; respiratory; response

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).

描述（由申请人提供）：先天性巨结肠是一种先天性肠动力障碍，由神经嵴迁移至胃肠道失败引起。神经克雷斯负责肠神经系统的形成，并且它们的缺失导致末端肠中的无神经节段，这导致不能促进蠕动收缩。该提案中描述的新观察结果导致了一种模型，其中基板细胞也迁移和定殖肠道，并选择性地产生内脏的内在感觉神经元。 肠神经节，而神经嵴细胞贡献于非感觉群体（运动神经元、中间神经元和神经胶质）。在这个应用程序中，我建议实验来定义肠神经系统中肠基板的命运，并解决内皮素和Ret信号如何控制神经嵴和基板细胞迁移和肠道定植。此外，我建议解决一个模型，其中肺神经丛的固有气道神经节也来自基板和神经嵴，这将提供新的见解先天性巨结肠症相关综合征，先天性中枢性低通气综合征（CCHS）的发病机制。