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: 6273803
• 负责人: JANE DODD
• 金额: $ 19.63万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-08 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6273803
• 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Rostrocaudal获取不同细胞命运的基础 发育中的神经管的轴。工作的重点是 腹部中线细胞组的分化，该组在尾部 区域，包括地板板，更稳定，跨越腹侧 前脑的中线。这些细胞在 神经背腹轴内细胞和轴突的图案 管，但在不同的腹侧细胞组的特性不同 沿着轴的尾部位置。在尾部，地板板 是通过来自下层轴向中胚层细胞的信号诱导的 脊索。在Rostral diencephalon中，中线细胞的诱导 似乎由不同的轴向中胚层控制 中胚层。此外，尽管信号分子，声音刺猬，但 介导地板板的诱导和分化 主脑前脑第二个信号传导因子BMP7需要作用 与声音刺猬的音乐会，显然使神经细胞敏感到声音 刺猬信号传导，以诱导具有延髓特征的细胞。目的 该提议要详细审查BMP7在结肠化中的作用 腹部中线并确定此基础的机制 BMP7和Sonic刺猬之间的新型相互作用。主要实验 工具将是体外外植体测定法，该测定允许神经的反应 板组织到来自中胚层的信号，并受到监测和操纵。 这些将与编码基因的小鼠结合使用 提出的分化途径的组成部分已经 在功能上灭活。实验将追踪 BMP7并将研究其对神经作用的潜在机制 组织。此外，我们将确定是否相关转录 因素在响应Sonic Hedgegog中介导的初始事件 中线细胞的不同种群。额外的可能性 代理参与腹部中线的鼻尾构图 延髓前脑和尾板板之间的区域将 也可以检查。 BMP功能阻滞的分布和作用 将研究蛋白质。这些实验在一起将导致 了解差异图案和 地板板和腹部中线细胞的性质 前脑。但是，他们还将更普遍地提供洞察力 进入神经组织的尾mautherting，揭示机制和 涉及定义神经轴的候选分子 盘子。