INDUCTION AND PATTERNING OF NEURAL TUBE VENTRAL MIDLINE

神经管腹侧中线的感应和图案化

• 批准号: 6565238
• 负责人: JANE DODD
• 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/6565238
• 关键词: biological signal transduction; brain regulatory center; cell differentiation; chick embryo; developmental neurobiology; diencephalon; embryo /fetus tissue /cell culture; gene deletion mutation; gene expression; gene induction /repression; gene interaction; genetic markers; immunocytochemistry; in situ hybridization; laboratory mouse; laboratory rat; mesoderm; monoclonal antibody; neural plate /tube; neurogenesis; neurogenetics; prosencephalon; transcription factor; vertebrate embryology

The overall goal of this work is to understand the molecular and cellular basis for the acquisition of distinct cell fates along the rostrocaudal axis of the developing neural tube. The focus of the work is the differentiation of the ventral midline cell group which, in caudal regions, comprises the floor plate and, more rostrally, spans the ventral midline of the rostral forebrain. These cells play major roles in the patterning of cells and axons within the dorsoventral axis of the neural tube but the properties of the ventral cell groups differ at different rostrocaudal positions along the axis. In caudal regions, the floor plate is induce by signals from the underlying axial mesoderm cells of the notochord. In rostral diencephalon, the induction of the midline cells appears to be controlled by different axial mesoderm, the prechordal mesoderm. Furthermore, although the signalling molecule, Sonic Hedgehog, mediates the induction and differentiation of the floor plate, in the rostral forebrain a second signalling factor, BMP7, is required to act in concert with Sonic Hedgehog, apparently sensitizing neural cells to Sonic Hedgehog signalling, to induce cells with rostral character. The aims of this proposal are to examine in detail the role of BMP7 in rostralization of the ventral midline and to determine the mechanisms underlying this novel interaction between BMP7 and Sonic Hedgehog. The main experimental tool will be in vitro explant assays, which permit the response of neural plate tissue to signals from mesoderm to be monitored and manipulated. These will be used in conjunction with mice in which genes encoding components of the proposed pathways of differentiation have been functionally inactivated. Experiments will trace the site of action of BMP7 and will investigate potential mechanisms of its action on neural tissue. In addition, we will determine whether related transcription factors mediate the initial events in response to Sonic Hedgehog in distinct populations of midline cells. The possibility that additional agents are involved in the rostrocaudal patterning of ventral midline regions intermediate between rostral forebrain and caudal floor plate will also be examined. The distribution and role of BMP function-blocking proteins will be studied. Together, these experiments will lead to an understanding of the mechanisms underling the differential patterning and properties of the floor plate and ventral midline cells of the rostral forebrain. In addition, however, they will provide insight more generally into rostrocaudal patterning of neural tissue, revealing mechanisms and candidate molecules that are involved in defining this axis of the neural plate.

这项工作的总体目标是了解分子和细胞 沿着吻尾侧获得不同细胞命运的基础 轴的发展神经管。工作的重点是 腹侧中线细胞群的分化，在尾侧 区域，包括底板，更吻，跨越腹侧 前脑嘴侧的中线这些细胞在免疫系统中起着重要作用。 神经元背腹轴内细胞和轴突的图案化 但腹侧细胞群的性质不同，在不同的 沿轴沿着吻尾位置。在尾部区域，底板 是由下面的轴向中胚层细胞的信号诱导的。 脊索在头端间脑，中线细胞的诱导 似乎是由不同的轴向中胚层， 中胚层此外，虽然信号分子，音速刺猬， 介导底板的诱导和分化， 吻侧前脑是第二个信号因子，BMP 7，需要发挥作用， 与Sonic Hedgehog的音乐会，明显使神经细胞对Sonic敏感 Hedgehog信号传导，以诱导具有喙特征的细胞。的目的 该提案将详细研究BMP 7在rostralization中的作用 的腹侧中线，并确定其背后的机制 BMP 7和Sonic Hedgehog之间的新相互作用。主要实验 工具将是体外外植体测定，其允许神经细胞的反应， 将组织置于来自中胚层的信号中进行监测和操作。 这些将与小鼠一起使用，其中基因编码 提出的分化途径的组成部分已经被 功能性失活。实验将追踪的作用部位 BMP7，并将研究其对神经细胞的作用的潜在机制。 组织.此外，我们将确定是否相关转录 因素介导的初始事件响应音速刺猬， 不同的中线细胞群。额外的可能性 代理人参与了腹中线的喙尾模式 在喙前脑和尾底板之间的中间区域将 也要检查。 BMP功能阻滞的分布及作用 蛋白质将被研究。总之，这些实验将导致一个 理解差异模式化的机制， 吻侧核底板和腹侧中线细胞的性质 前脑此外，他们将提供更普遍的见解， 神经组织的喙尾模式，揭示机制， 参与定义神经轴的候选分子 板