NEURONAL CELL DETERMINATION IN THE PNS

PNS 中的神经细胞测定

• 批准号: 6394259
• 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/6394259
• 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(逐字摘自申请者摘要)：受监管的发展 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脊的前体是如何 分化是在发育过程中控制的，以及神经元的适当程度 与外围的靶组织相匹配。此应用程序侧重于 痛觉、降钙素基因相关的发育调控 背根神经节(DRG)内含CGRP的感觉神经元。 含降钙素基因相关肽的感觉神经元与皮肤和肠道周围靶组织接触 在调节痛觉和局部皮肤炎症中起着关键作用。 这个项目是基于我们新颖的观察到的成员的转变 生长因子β家族--包括激活素和骨形态发生蛋白 (BMPS)--诱导包括CGRP表达的痛觉表型 体外培养。我们推测，皮肤、血液中的特定TGFb家族配体 血管和肠靶组织诱导感觉性痛觉表型 发育过程中的神经元。本应用程序中的研究将测试这一点 使用体外和体内功能分析的假说。打招呼和 卵泡抑素将被用来识别CGRP背后的配体类别 皮肤细胞系因子诱导。将对本地人的皮肤和肠道进行检测 体外生物活性和配体，使用细胞开发的分析方法 台词。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 生物活性因素是存在的。TGFb家族配体在体内的作用将是 通过病毒错误表达配体、抑制物或BMP受体进行检测。《长河》 这些研究的术语目标是了解调节 神经元分化。即使在背根节内，神经元相对较少 类型的出现，对于是什么调节不同类型的 神经元是由神经脊细胞产生的。完成拟议的 研究将促进我们对目标派生的重要性的理解 生长因子，特别是TGFb家族配体激活素和骨 形态发生蛋白在确定胚胎感觉神经元类型中的作用 先驱物。