Placode lineage contribution to Hirschsprung's disease

基板谱系对先天性巨结肠的贡献

基本信息

批准号：
8562612
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
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-06-01 至 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8562612
关键词：
Accounting 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 Image In Vitro Interneurons Intestines Lead Ligands Logic Lung Maps 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 base cell motility cellular targeting congenital central hypoventilation syndrome defined contribution in vivo insight migration motility disorder nerve stem cell nervous system development nervous system disorder novel progenitor public health relevance receptor relating to nervous system research study respiratory response

项目摘要

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）：Hirschsprung病是一种先天性肠道运动，是由神经rest迁移到胃肠道的失败引起的。神经CRE负责形成肠神经系统，它们的缺失导致末端肠中的Aganglionic片段，这导致未能促进蠕动收缩。该提案中描述的新观察结果导致了一个模型，在该模型中，Placode细胞也迁移和定居肠道，并有选择地引起了固有的感觉神经元肠神经节，而神经rest细胞有助于非感官人群（运动神经元，中间神经元和神经胶质）。在此应用中，我提出了实验，以定义肠神经系统中肠上置的命运，并解决内皮素和RET信号如何控制肠道的神经Crest和Placode细胞迁移以及肠道的定殖。此外，我建议解决一个模型，在该模型中，肺丛的内在气道神经节也源自Placode和Neural Crest，该模型将为Hirschsprung疾病相关综合征，先天性中心中枢性低文化综合征（CCHS）提供新的洞察力。