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

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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.