Cell Motility and Cell Interactions During Neurulation

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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.