Axonal death 4: Shared Mechanisms of Axon Regeneration and Degeneration
An injured or diseased axon has two choices: degenerate or regenerate. In the compromised central nervous system, regeneration is inhibited and degeneration is promoted, resulting in irreparable loss of neuronal function. How these two contrasting processes are coordinately regulated is not well understood. To address this question, we developed a novel in vivo injury model to screen for mutations that disrupt the balance between regeneration and degeneration of injured GABA axons. In this model, motor axons are severed into a proximal fragment that remains attached to the cell body and a distal fragment that is separated from the cell body. We identified a mutant strain with increased regeneration of the proximal segment, decreased degeneration of the distal segment, and improved functional recovery after injury. To coordinately inhibit axon regeneration of one fragment and promote degeneration of the other, the identified gene functions intrinsically in each to regulate divergent downstream genetic pathways on either side of the injury. Our findings present a potential opportunity to tilt the balance between degeneration and regeneration towards repair of the injured and diseased nervous system.