Mechanisms of neural tube closure

神经管闭合是一个形态发生过程，涉及复杂的行为 极化的神经板细胞。有200多个基因参与了这一过程 遗传模型，神经管畸形是人类最常见的出生方式之一 缺陷。然而，神经管关闭的机制仍然知之甚少。 现有的脊椎动物模型有限。我们的初步实验已经确定了一种 非洲爪哇神经板面上几种蛋白质的独特极化 证明了这种极性需要平面细胞极性(PCP)的函数 和顶端-基底极性蛋白。拟议的研究将对 神经板使用一种新型的荧光传感器。物理上相互关联的新分子 将使用一种新的邻近和互补来识别PCP复合体- 基于生物素化结合质谱学的方法。该组织的参与 神经管关闭期间PCP信号中的心尖-基底极性蛋白也将 已评估。非洲爪哇胚胎在任何发育阶段都很容易获得，而且 独一无二地适用于这些研究，允许快速分析蛋白质定位和 通过生物化学、胚胎学和细胞生物学的组合发挥作用 接近了。这些实验将阐明基本的信号机制， 是中枢神经系统正常发育的基础。建议进行的研究包括 与人类健康高度相关，因为这些信号通路的错误调节 会导致大脑和神经管缺陷以及各种神经疾病。-- 。

Neural tube closure is a morphogenetic process that involves complex behaviors of polarized neural plate cells. With more than 200 genes implicated in this process in genetic models, neural tube abnormalities are among the most common human birth defects. Nevertheless, mechanisms of neural tube closure remain poorly understood and the available vertebrate models are limited. Our preliminary experiments have identified a unique polarization of several proteins in the plane of the Xenopus neural plate and demonstrated that this polarity requires the functions of both planar cell polarity (PCP) and apical-basal polarity proteins. The proposed studies will carry out live imaging of the neural plate using a novel fluorescent sensor. New molecules that physically associate with the PCP complex will be identified using a novel proximity- and complementation- based biotinylation approach combined with mass spectrometry. The involvement of the apical-basal polarity proteins in PCP signaling during neural tube closure will also be evaluated. Xenopus embryos are easily accessible at any developmental stage and are uniquely suited for these studies, allowing rapid analysis of protein localization and function through a combination of biochemical, embryological and cell biological approaches. These experiments will shed light on basic signaling mechanisms that underlie normal development of the central nervous system. The proposed studies are highly relevant to human health, because misregulation of these signaling pathways leads to brain and neural tube defects and a variety of neurological disorders.   .