How are Regenerating Axons Guided in the Adult Nervous System

PROJECT SUMMARY Common nerve injuries often lead to long-term disabilities in the central nervous system and in the peripheral nervous system with increased adult age. Understanding how axon guidance is regulated in the mature nervous system is critical to understanding how the nervous system changes after development and to developing therapies aimed at reestablishing proper neural circuitry across lesions. Caenorhabditis elegans is a highly tractable model to dissect conserved molecular and cellular mechanisms that regulate axon regeneration and axon guidance. With this system, I have identified an extracellular matrix protein that guides regenerating motor axons specifically in the post-development nervous system and is required for functional recovery. I will apply my developing skills in detailed genetic analyses, laser axotomy, in vivo imaging, sequencing, and bioinformatics to further determine the post-developmental specific role of this protein in axon guidance. In addition to providing a critical advance in understanding the fundamental mechanisms of axon guidance, it will also inform future therapeutic approaches that can be manipulated to promote targeted axon guidance in the injured adult nervous system.