The roles of afadin in motor neuron development and assembly of spinal motor circuits

这项建议旨在阐明神经系统在发育过程中组装的分子和解剖学要求。具体地说，我们将定义脊髓运动神经回路中运动神经元定位和输入/输出连接专一性之间的关系。这将通过分析afadin在运动神经元组织和运动电路组装中的作用来实现，如下两个具体目标所述。afadin是一种参与胶凝素和钙粘附素黏附信号的支架分子。这些研究将为指导神经回路连接的分子机制提供洞察力，并将阐明afadin信号在细胞-细胞黏附识别控制中的作用。目的1.缺乏afadin功能的运动神经元的发育。1A)运动神经元生成和定位的发育分析。1B)运动神经元与肌肉连接的特异性分析。1C)确定afadin和钙粘蛋白/连环蛋白信号在运动神经元发育中的相对贡献。目的2.缺乏afadin功能的感觉-运动神经回路的组装。2A)感觉到运动神经元连接的特异性分析。2B)运动神经元前连接的分析电路组织。2C)定义运动神经元位置在感觉-运动电路组装中的作用。

This proposal aims at elucidating the molecular and anatomical requirements underlying the assembly of the nervous system during development. Specifically, we will define the relationship between motor neuron positioning and input/output connection specificity in spinal motor circuits. This will be achieved by analyzing the role of afadin, a scaffold molecule involved in nectins and cadherins adhesive signaling, in motor neuron organization and motor circuit assembly as detailed in the two specific aims below. These studies will provide insights into the molecular mechanisms directing the wiring of neural circuits and will clarify the contribution of afadin signaling in the control of cell-cell adhesive recognition.Aim 1. Motor neuron development in absence of afadin function.1A) Developmental analysis of motor neuron generation and positioning.1B) Analysis of motor neuron to muscle connection specificity.1C) Defining the relative contributions of afadin and cadherin/catenin signaling in motor neuron development.Aim 2. The assembly of sensory-motor circuits in absence of afadin function.2A) Analysis of sensory to motor neuron connection specificity.2B) Analysis of pre-motor neuron circuit organization.2C) Defining the role of motor neuron position in the assembly of sensory-motor circuits.