NEURONAL CELL DETERMINATION IN THE PNS

PNS 中的神经细胞测定

• 批准号: 6639607
• 负责人: ALISON K HALL
• 金额: $ 30.6万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-06 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6639607
• 关键词: calcitonin gene related peptide; chick embryo; developmental neurobiology; gene expression; laboratory rat; neurogenesis; peripheral nervous system; sensation; spinal ganglion; transforming growth factors

DESCRIPTION(Verbatim from applicant's abstract): Regulated development of the sensory nervous system results in the ability to feel pain and to sense body position. A major challenge has been to understand how neural crest precursor differentiation is controlled during development and how appropriate neurons are matched with target tissues in the periphery. This application focuses on the developmental regulation of the pain-sensing, calcitonin gene related peptide (CGRP)-containing sensory neurons in the dorsal root ganglion (DRG). CGRP-containing sensory neurons contact skin and gut peripheral target tissues and play pivotal roles in mediating pain sensation and local skin inflammation. This project is based on our novel observation that members of the transforming growth factor beta family -- including activins and bone morphogenetic proteins (BMPs) -- induce the pain sensing phenotype that includes CGRP expression in vitro. We hypothesize that specific TGFb family ligands from skin, blood vessel and gut target tissues induce the pain-sensing phenotype in sensory neurons during development. Studies in this application will test this hypothesis using both in vitro and in vivo functional assays. Noggin and follistatin will be used to identify classes of ligands that underlie CGRP induction by skin cell line factors. Native skin and gut will be assayed for biological activity and ligands in vitro, using assays developed with cell lines. The spatial and temporal localization of ligands and inhibitors will be carried out at critical periods of target contact to learn where and when bioactive factors are present. The role of TGFb family ligands in vivo will be tested by viral misexpression of ligand, inhibitor or BMP receptor. The long term objective of these studies is to understand the mechanisms that regulate neuronal differentiation. Even within the DRG, where relatively few neuronal types arise, little is known about what regulates how different types of neurons are generated from neural crest cells. The completion of the proposed studies will advance our understanding of the importance of target derived growth factors, and in particular the TGFb family ligands activin and bone morphogenetic proteins, in specifying sensory neuronal types from embryonic precursors.

描述（来自申请人摘要的逐字记录）： 感觉神经系统导致感觉疼痛和感觉身体的能力 位置一个主要的挑战是了解神经嵴前体是如何 分化是在发育过程中控制的， 与周围的靶组织相匹配。本申请集中于 痛敏、降钙素基因相关的发育调控 背根神经节（DRG）中含有CGRP的感觉神经元。 含CGRP的感觉神经元接触皮肤和肠道外周靶组织 并在介导疼痛感觉和局部皮肤炎症中起关键作用。 这个项目是基于我们的新观察， 生长因子β家族--包括激活素和骨形态发生蛋白 （骨形成蛋白）-诱导疼痛感应表型，包括CGRP表达， 体外我们假设，来自皮肤、血液、 血管和肠靶组织诱导感觉神经元的痛觉感受表型， 神经元在发育过程中本申请中的研究将测试这一点 假设使用体外和体内功能测定。Noggin和 卵泡抑素将被用来鉴定CGRP的配体类型 通过皮肤细胞系因子诱导。将测定天然皮肤和肠道的 体外生物活性和配体，使用用细胞开发的测定法 线配体和抑制剂的空间和时间定位将是 在与目标接触的关键时期进行，以了解何时何地 存在生物活性因子。TGFb家族配体在体内的作用将是 通过配体、抑制剂或BMP受体的病毒错误表达进行测试。长 这些研究的长期目标是了解调节 神经元分化即使在DRG内，相对较少的神经元 类型的出现，很少有人知道是什么调节如何不同类型的 神经元由神经嵴细胞产生。完成建议 研究将促进我们对目标衍生的重要性的理解， 生长因子，特别是TGF β家族配体激活素和骨 形态发生蛋白，在指定胚胎感觉神经元类型中的作用 前体