TGF-BETA FAMILY ROLE IN PATTERNING IN VERTEBRATE CNS

底板是一个暂时性的上皮细胞群，它开始 在神经板的中线进行区分，然后占据 神经管腹中线与中枢神经系统发育 (CNS)。最近的研究表明，地板上的细胞有一个 在脊椎动物中枢神经系统的早期发育中起核心作用。地板 板块和下面的脊索似乎控制着 细胞沿神经背腹轴线的分化模式 管，也可能有助于神经板的区域化 沿着它的前后轴线。后来，地板似乎引导着 中枢神经元子集的轴突 促进轴突生长和定向的化学诱导剂 体外和体内。此外，地板看起来像是一个 参与接触相关轴突引导的中间靶点 穿过中枢神经系统的腹中线。 支撑地板这些细胞功能的分子机制 板块特征仍然不佳。为了尝试分析分子 根据楼板的功能，我们已经开始识别新的楼板 特定于平板的文字记录。使用一种新的差减杂交策略 我们已经分离出了几个底板富含或特定的cDNA和 用原位杂交法检测它们的分布。在此应用程序中 我们建议进行一系列实验来确定身份和 底板特异基因的功能。其中一个基因已经 在新的可扩散蛋白上克隆并鉴定了编码蛋白Fp5 与与细胞黏附有关的蛋白质有惊人的同源性， 趋化性和触觉趋性。我们将研究FP5的功能 蛋白质，关注其在神经细胞控制中的潜在作用 分化与轴突生长和引导。此外，我们还将 完成另外两个楼层的结构和功能表征 使用类似的分析方法检测平板特异性基因。最后，我们将使用精炼 差减杂交法鉴定附加底板 可能参与发育信号传递的特定基因 楼板的属性。 从这些研究中得出的信息应该会提供一个更清晰的 对控制细胞和分子机制的理解 脊椎动物中枢神经系统的早期发育。

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.