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: 6296945
• 负责人: JANE DODD
• 金额: $ 20.63万
• 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: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6296945
• 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 沿轴尾部获得不同细胞命运的基础 发育中的神经管的轴。工作重点是 腹侧中线细胞群的分化，在尾部 区域，包括底板，并且更靠近嘴侧，跨越腹侧 前脑吻端中线。这些细胞在 神经背腹轴内细胞和轴突的模式 管，但腹侧细胞群的特性在不同的情况下有所不同 沿轴的轴尾位置。在尾部区域，底板 是由来自底层轴向中胚层细胞的信号诱导的 脊索。在头侧间脑中，中线细胞的诱导 似乎是由不同的轴向中胚层控制的 中胚层。此外，虽然信号分子 Sonic Hedgehog 介导底板的诱导和分化， 前脑前脑需要第二个信号因子 BMP7 来发挥作用 与 Sonic Hedgehog 的音乐会，显然使神经细胞对 Sonic 敏感 Hedgehog 信号传导，诱导具有吻端特征的细胞。的目标 该提案旨在详细研究 BMP7 在 rostralization 中的作用 腹侧中线并确定其背后的机制 BMP7 和 Sonic Hedgehog 之间的新颖互动。主要实验 工具将是体外外植体测定，它允许神经反应 板组织与来自中胚层的信号进行监测和操作。 这些将与编码基因的小鼠结合使用 所提出的分化途径的组成部分已被 功能失活。实验将追踪作用位点 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 因素介导响应 Sonic Hedgehog 的初始事件 不同的中线细胞群。额外的可能性 代理参与腹侧中线的轴尾模式 前脑和尾底板之间的中间区域 也予以检查。 BMP功能阻断的分布和作用 将研究蛋白质。这些实验共同将导致 了解差异模式背后的机制和 底板和吻端腹侧中线细胞的特性 前脑。然而，此外，他们还将提供更普遍的见解 研究神经组织的轴尾模式，揭示机制和 参与定义神经轴的候选分子 盘子。