Genetic Analysis of Glial Contribution to Peripheral Nervous System Assembly

 描述（由申请人提供）：运动神经在将信息从中枢神经系统分流到外周靶点方面起着关键作用。它们的形成需要不同细胞成分的协调发展，包括运动轴突、包裹它们的神经胶质细胞和周围的肌肉。在神经系统构建过程中，这些细胞必须长距离迁移并协调其分化，以确保电信息的有效传播。在这个项目中，我们将研究神经束膜胶质细胞在早期脊髓运动神经发育中的作用，以及周围神经发育和疾病过程中肌肉-神经相互作用的作用。尽管脊髓运动轴突以沿着脊椎动物神经元的前-后轴的定型位置离开脊髓， 管和神经嵴流到这些位置，预示这些出口点的机制知之甚少。在本项目的目标1中，我们将研究神经束膜胶质细胞及其前体预示运动出口点（MEP）和直接运动轴突生长和神经嵴迁移的假设。在目标2中，我们将研究肌营养不良蛋白在早期 神经系统发育在杜氏肌营养不良症（DMD）的斑马鱼模型。在斑马鱼中耦合遗传学和体内成像，我们可以：1）清楚地梳理出 运动神经发育，2）阐明它们是如何调节的，3）为更基本地理解形成功能性神经系统的规则奠定基础，4）阐明疾病中可能受到干扰的机制。

 DESCRIPTION (provided by applicant): Motor nerves play the critical role of shunting information out of the central nervous system to targets in the periphery. Their formation requires the coordinated development of distinct cellular components, including motor axons, the glial cells that ensheath them and surrounding muscle. During nervous system construction, these cells must migrate long distances and coordinate their differentiation, ensuring the efficient propagation of electrical information. In this project, we will investigate the role of perineurial glia in early spinal motor nerve development as well as the role of muscle-nerve interactions during peripheral nerve development and disease. Although spinal motor axons exit the spinal cord in stereotyped positions along the anterior-posterior axis of the vertebrate neural tube and neural crest streams to these locations, the mechanisms that prefigure these exit points are poorly understood. In Aim 1 of this project, we will investigate the hypothesis that perineurial glia and their precursors prefigure motor exit points (MEP) and direct motor axon outgrowth and neural crest migration. In Aim 2, we will investigate the role of dystrophin in early nervous system development in a zebrafish model of Duchenne Muscular Dystrophy (DMD). Coupling genetics and in vivo imaging in the zebrafish, we can: 1) distinctly tease apart facets of motor nerve development, 2) elucidate how they are regulated, 3) lay the groundwork for a more fundamental understanding of the rules that form a functional nervous system and 4) shed light on mechanisms that could be perturbed in disease.