Cellular Mechanisms of Neurite Outgrowth and Guidance

Functional recovery from peripheral nerve injury hinges on the ability of neurons within the nerve bundle to re-grow damaged neurites (axons and dendrites) and to reestablish connections with the specific targets they innervate. While the capacity for re-growth exists, and can in fact be extensive, the ability of the regenerating neurite to successfully navigate a course back to targets more that a few millimeters away is typically limited. Biological studies have established that the growth cone, a motile structure at the leading tip of the neurite, is the primary site at which navigational decisions are made. Little is known about growth cone dynamics or their specific contributions to neurite outgrowth and guidance. This project proposes a conceptual framework for investigating cellular events occurring at the growth cone and their effects on developing neurite trajectory in the presence or absence of directional guidance cues. This work is to provide a means for bridging the existing gap between current experimental approaches to the understanding of nerve growth, and the available theoretical tools that could serve to speed the progress of nerve regeneration research.