A fundamental question in neurobiology is how axons respond to injury and disease. Damaged neurons can sometimes repair themselves by a process called axon regeneration. However, many neurons do not regenerate, often resulting in permanent deficits following nerve injury. Clinical strategies to repair the injured nervous system are lacking because the mechanisms that determine whether an injured axon will functionally regenerate are poorly understood. Therefore, determining the mechanisms that regulate individual components of the regeneration response, including those that determine whether an injured axon will regenerate and whether it will reform functional synapses (functional axon regeneration), is critical to understanding how to improve functional recovery after injury. To reach this goal we are investigating how a number of genes that we recently identified as regulators of functional axon regeneration determine whether an injured axon will we repaired. Our approach is to take advantage of the powerful C. elegans model of axon regeneration, which has a highly conserved genome, is genetically tractable, and in which functional axon regeneration can be studied in vivo and with single axon resolution, to perform detailed genetic analyses, laser axotomy, imaging, and behavioral assays. Answering the above questions is essential to our understanding of functional axon regeneration in the adult nervous system and will significantly enhance our understanding of how to elicit regeneration and restore function to damaged neurons.
Many axons do not regenerate and reform functional synapses with their target cells after nerve injury, a process called functional axon regeneration, often resulting in permanent deficits. The mechanisms that determine whether an injured axon will functionally regenerate are poorly understood. By determining how recently identified enhancers of functional axon regeneration regulate repair of the injured nervous system, this proposal will add significantly to our understanding of how an adult axon regulates its response to injury, which is critical for designing effective strategies to repair the injured nervous system.
