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（申请人摘要的逐字记录）：规范开发 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如何 分化在发育过程中受到控制以及神经元如何适当地控制 与周围的目标组织相匹配。该应用程序重点关注 痛觉、降钙素基因相关的发育调节 背根神经节（DRG）中含有肽（CGRP）的感觉神经元。 含有 CGRP 的感觉神经元接触皮肤和肠道周围靶组织 在介导疼痛感和局部皮肤炎症中发挥关键作用。 该项目基于我们的新颖观察，即转型成员 生长因子β家族——包括激活素和骨形态发生蛋白 (BMP)——诱导疼痛感知表型，包括 CGRP 表达 体外。我们假设来自皮肤、血液的特定 TGFb 家族配体 血管和肠道靶组织诱导感觉痛觉表型 发育过程中的神经元。本应用程序的研究将对此进行测试 使用体外和体内功能测定的假设。诺金和 卵泡抑素将用于识别 CGRP 背后的配体类别 由皮肤细胞系因子诱导。将对原生皮肤和肠道进行检测 使用细胞开发的测定法进行体外生物活性和配体 线。配体和抑制剂的空间和时间定位将是 在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。长的 这些研究的长期目标是了解调节机制 神经元分化。即使在 DRG 内，神经元相对较少 类型的出现，人们对什么调节不同类型的机制知之甚少。 神经元由神经嵴细胞产生。拟议的完成情况 研究将增进我们对目标衍生的重要性的理解 生长因子，特别是 TGFb 家族配体激活素和骨 形态发生蛋白，在胚胎中指定感觉神经元类型 前体。