Cell Motility and Cell Interactions During Neurulation

描述(由申请人提供)：主要目的是确定组织 控制特定类型极化的相互作用和信号通路 在“汇聚和延伸”期间发生的细胞运动(变窄和伸展 非洲爪蛙胚胎神经系统的伸长运动 并测试这种运动性在神经管形成中的作用。过去时 研究发现，导致神经细胞运动的单极、中间方向的细胞运动 细胞相互插入，从而使细胞变窄和拉长 神经板。以前未知的来自中线组织的信号 脊索/脊板被发现控制这种极化的运动，并且一个 开发了中线如何调节这种运动性的模型。这个 建议的研究使用最先进的荧光细胞标记，荧光 显微镜和数字成像方法描述培养的细胞运动 外植体，并在胚胎组织的重组中，旨在测试 假想控制极化细胞的特定组织相互作用 能动性。 被认为控制这种运动性的分子的分子微扰将是 在特定的时间靶向特定的细胞，使用X。 Levis和果蝇的Ga14/UAS系统。具体目标是：1. 进一步刻画深神经板的极化和定向运动 细胞和来自中线组织的信号诱导这种运动，使用 我们的模型作为实验的指导；2)确定平面单元的作用 调节这种极化定向细胞行为的极性途径；3) 确定小GTP酶在神经细胞运动控制中的作用 板块形态发生。这项工作将提供对细胞的更深入的了解 脊椎动物中形成神经管的运动性，以及这种运动性是如何 由特定的组织相互作用和信号通路控制。这些 这些发现将有助于理解人类出生缺陷的失败， 如脊柱裂，神经不能正常形成和闭合。

DESCRIPTION (provided by applicant): The broad aim is to determine the tissue interactions and signaling pathways that control a specific type of polarized cell motility that occurs during "convergence and extension" (narrowing and elongation) movements of the embryonic nervous system of the frog, Xenopus laevis, and to test the role of this motility in forming the neural tube. Past work identified a monopolar, medially-directed cell motility that causes neural cells to intercalate between one another, thus narrowing and elongating the neural plate. Previously unknown signals from the midline tissues of notochord/notoplate were discovered to control this polarized motility, and a model of how this motility is regulated by the midline was developed. The proposed research uses state of the art fluorescent cell labeling, fluorescence microscopy, and digital imaging methods to describe cell movements in cultured explants, and in recombinations of embryonic tissues, designed to test the specific tissue interactions hypothesized to control the polarized cell motility. Molecular perturbations of molecules thought to control this motility will be targeted to specific cells at specific times, using transgenic lines of X. laevis and the Ga14/UAS system from Drosophila. The specific aims are to: 1. further characterize the polarized and oriented motility of deep neural plate cells and the signals from the midline tissues that induce this motility, using our model as a guide for experiments; 2) determine the role of the planar cell polarity pathway in regulating this polarized and oriented cell behavior; 3) determine the role of small GTPases in controlling cell motility in neural plate morphogenesis. This work will provide a deeper understanding of the cell motility that forms the neural tube in vertebrates, and how this motility is controlled by specific tissue interactions and signaling pathways. These findings will contribute to understanding the failure of human birth defects, such as spina bifida, in which the neural does not form and close properly.