TGF-BETA FAMILY ROLE IN PATTERNING IN VERTEBRATE CNS

TGF-β 家族在脊椎动物 CNS 模式中的作用

• 批准号: 6565240
• 负责人: Thomas M. Jessell
• 金额: $ 25.59万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-01 至 2002-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6565240
• 关键词: biological signal transduction; brain regulatory center; cell differentiation; cell type; cerebellum; chick embryo; developmental neurobiology; gene expression; gene induction /repression; gene targeting; genetically modified animals; glia; laboratory mouse; molecular cloning; mutant; neural plate /tube; neurogenesis; neurogenetics; phenotype; polymerase chain reaction; southern blotting; transcription factor; transfection /expression vector; transforming growth factors; vertebrate embryology

The floor plate is a transient epithelial cell group which begins to differentiate at the midline of the neural plate and later occupies the ventral midline of the neural tube and developing central nervous system (CNS). Recent studies indicate that cells of the floor plate have a central role in the early development of the vertebrate CNS. The floor plate, together with the underlying notochord, appears to control the pattern of cell differentiation along the dorsoventral axis of the neural tube, and may also contribute to the regionalization of the neural plate along its anteroposterior axis. Later, the floor plate appears to guide the axons of a subset of central neurons by releasing a diffusible chemoattractant which promotes the outgrowth and orientation of axons in vitro and in vivo. In addition, the floor plate appears to act as an intermediate target involved in the contact-dependent guidance of axons that cross the ventral midline of the CNS. The molecular mechanism that underlie these cellular functions of the floor plate remain poorly characterized. In an attempt to analyze the molecular basis of floor plate function we have begun to identify the novel floor plate-specific transcripts. Using a new subtractive hybridization strategy we have isolated several floor plate enriched or specific cDNAs and assessed their distribution by in situ hybridization. In this application we propose to perform a series of experiments to determine the identity and function of floor plate specific genes. One of the genes that has already been cloned and characterized, FP5, encodes on novel diffusible protein with striking homologies to proteins implicated in cell adhesion, chemotaxis and haptotaxis. We will examine the function of the FP5 protein, focussing on its potential roles in the control of neural cell differentiation and axon growth and guidance. In addition, we will complete the structural and functional characterization of two other floor plate-specific genes using similar assays. Finally, we will use refined subtractive hybridization methods to identify additional floor plate specific genes that may be involved in the developmental signalling properties of the floor plate. The information that derives from these studies should provide a clearer understanding of the cellular and molecular mechanisms that control the early development of the vertebrate central nervous system.

底板是一个短暂的上皮细胞群，它开始 在神经板的中线分化，后来占据了 神经管的腹侧中线和发育中的中枢神经系统 （CNS）。 最近的研究表明，地板的细胞具有 在脊椎动物中枢神经系统的早期发育中起重要作用。 地板 板，连同下面的脊索，似乎控制 细胞分化的模式沿着背腹轴的神经 管，也可能有助于神经板的区域化 沿着其前后轴。 后来，地板出现了引导 通过释放可扩散的物质来刺激中枢神经元子集的轴突 化学引诱物，促进轴突的生长和定向， 体外和体内。 此外，地板似乎充当了 参与轴突接触依赖性导向的中间靶点 穿过中枢神经系统腹侧中线 地板细胞功能的分子机制 板仍然不好表征。 在试图分析分子 根据地板的功能我们已经开始确定新颖的地板 平板特异性转录物。 使用新的消减杂交策略 我们已经分离了几种底板富集的或特异性的cDNA， 通过原位杂交评估它们的分布。 本申请中 我们建议进行一系列实验来确定身份， 底板特异性基因的功能。 其中一个基因已经 FP5基因编码一种新的可扩散蛋白 与涉及细胞粘附的蛋白质具有惊人的同源性， 趋化性和趋触性。 我们将研究FP5的功能 蛋白质，侧重于其在控制神经细胞的潜在作用， 分化和轴突生长和引导。 此外，我们将 完成另外两层的结构和功能表征 板特异性基因使用类似的测定。 最后，我们将使用 消减杂交法鉴定附加底板 可能参与发育信号传导的特定基因 地板的特性。 从这些研究中获得的信息应该提供一个更清晰的 了解控制细胞和分子机制， 脊椎动物中枢神经系统的早期发育。