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 沿吻尾获得不同细胞命运的基础 发育中的神经管的轴。工作的重点是 尾侧腹侧中线细胞群的分化 区域由底板组成，更具喙的是横跨腹侧 前脑吻部的中线。这些细胞在脑组织中起主要作用 神经背腹侧轴内细胞和轴突的构型 管，但腹侧细胞组的性质不同 沿轴线的肩尾位置。在尾部，底板 是由下层中轴中胚层细胞发出的信号诱导的 弦乐。在吻侧间脑，中线细胞的诱导 似乎是由不同的轴向中胚层控制的，即前索 中胚层。此外，尽管信号分子Sonic Hedgehog， 介导底板的诱导和分化，在 吻侧前脑还需要第二个信号因子BMP7来发挥作用 与Sonic Hedgehog合作，显然使神经细胞对Sonic敏感 刺猬信号，诱导具有喙特征的细胞。的目标是 这项提议是为了详细研究BMP7在吻化中的作用 腹中线并确定其背后的机制 BMP7与Sonic Hedgehog之间的新相互作用。主要的实验 工具将是允许神经反应的体外外植体试验。 从中胚层到板状组织的信号被监测和操纵。 这些基因将与小鼠一起使用，在小鼠中编码基因 所提出的分化途径的组成部分包括 功能失活的。实验将会追踪到 Bmp7，并将研究其对神经作用的潜在机制 组织。此外，我们将确定相关转录是否 影响Sonic Hedgehog首发事件的因素 不同的中线细胞群。另一种可能性是 神经递质参与腹侧中线吻尾模式的形成 前脑吻侧和尾侧底板之间的中间区域 也要接受检查。骨形态发生蛋白功能阻断的分布和作用 将对蛋白质进行研究。总而言之，这些实验将导致 对不同图案的基础机制的理解 吻部底板和腹中线细胞的特性 前脑。然而，除此之外，它们将提供更广泛的洞察力 神经组织的肩尾模式，揭示了机制和 参与定义神经轴的候选分子 盘子。