DESCRIPTION: The objective of this grant is to define the role played by the signaling molecule collapsin-1 (semD, sema-III) in the developing nervous system. Collapsin-1 induces the collapse and paralysis of sensory growth cones and in collagen stabilized cultures acts as a repellent for sensory axons. During the course of the current funding period, the PI has compared the relative distributions of collapsin-1 expression with the trajectories of axon that are responsive to it. These studies have suggested that collapsin-1 plays a role in organizing axon trajectories in the skin, spinal cord, hindbrain, olfactory bulb and cerebellum. The PI will test these expectations by manipulating collapsin-1 function in vivo using a variety if misexpression, knockout and dominant negative strategies. Specifically, he will: Aim 1: study the guidance of selected axons in collapsin-1 knockout mice; Aim 2: study the relationship between the structure and function of the collapsin-1 receptor component neuropilin; and; Aim 3: study the role of collapsin-1 mediated guidance in chick embryos. Identifying repellent cues and understanding their roles in normal development may be an essential step towards obtaining axonal repair and establishing appropriate connectivity in damaged nervous tissue.