Cell Motility and Cell Interactions During Neurulation

广泛的目的是确定控制特定类型的组织相互作用和信号通路。 极化细胞运动发生在“收敛和延伸”（缩小和伸长）运动， 胚胎神经系统的青蛙，非洲爪蟾loevis，并测试这种运动的作用，在形成 神经管过去的工作确定了一个单极，介导的细胞运动，导致神经细胞嵌入 彼此之间，从而缩小和拉长神经板。此前未知的信号来自 脊索/背板的中线组织被发现控制这种极化运动，以及这种极化运动是如何发生的模型。 运动是由中线调节的。拟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外植体中的细胞运动， 以及胚胎组织的重组，旨在测试特定的组织相互作用， 控制极化的细胞运动。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. Loevis和Gal 4/UAS系统 果蝇具体目标是：1.进一步表征深层神经元的极化和定向运动， 板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指导， 2）确定平面细胞极性通路在调节这种极化和定向细胞中的作用 3）确定小GTP酶在神经板形态发生中控制细胞运动的作用。这 这项工作将提供对形成脊椎动物神经管的细胞运动的更深入的理解，以及这种运动是如何形成的。 运动性由特定的组织相互作用和信号传导途径控制。这些发现将有助于 了解人类先天缺陷的失败，如脊柱裂，其中神经不能形成和关闭， 正常

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" (narrowingand elongation) movements of the embryonic nervous system of the frog, Xenopus loevis, 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 recombinataions 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. loevis and the Gal4/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 pathwayin 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 whichthe neural does not form and close properly.