Cell Motility and Cell Interactions During Neurulation

描述（由申请人提供）：主要目的是确定组织 控制特定类型的极化的相互作用和信号通路 在“会聚和伸展”（变窄和扩张）期间发生的细胞运动 延伸）运动的胚胎神经系统的青蛙，爪蟾 laevis，并测试这种运动在形成神经管中的作用。过去 工作确定了一个单极，介导的细胞运动，导致神经 细胞之间相互插入，从而缩小和延长 神经板以前未知的信号从中线组织的 脊索/背板被发现控制这种极化运动， 这种运动性是如何由中线调节的模型被开发出来。的 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来描述培养的细胞运动， 外植体，并在胚胎组织的重组，旨在测试 假设特定组织相互作用控制极化细胞 能动性 被认为控制这种运动性的分子的分子扰动将是 在特定时间靶向特定细胞，使用X. laevis和果蝇的Ga 14/UAS系统。具体目标是：1. 进一步表征深部神经板的极化和定向运动 细胞和来自中线组织的诱导这种运动的信号，使用 我们的模型作为实验的指导; 2）确定平面细胞的作用 极性通路调节这种极化和定向细胞行为; 3） 确定小GTP酶在控制神经细胞运动中的作用， 板块形态发生这项工作将提供对细胞更深入的了解 在脊椎动物中形成神经管的运动，以及这种运动是如何 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， 例如脊柱裂，其中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.