Improving functional axon regeneration in the injured nervous system

To fully repair injured neurons, our nervous systems must both regenerate damaged axons and rebuild synapses with interacting cells, a process called functional axon regeneration. However, many injured axons, especially those in the central nervous system, actively inhibit functional axon regeneration, resulting in a permanent loss of motor and sensory function. Identifying and characterizing these molecular mechanisms that inhibit functional axon regeneration is critical to understanding how to repair the injured adult nervous system. To do so, we use a genetically tractable C. elegans model in which axon regeneration and degeneration can be studied in vivo with single axon resolution. I will present our recent findings of signal transduction pathways that function intrinsically and independently of one another to regulate axon regeneration, synapse reformation, and degeneration after injury. These include poly (ADP-ribosylation) and TIR-1/SARM signaling. Defining how these pathways regulate a neuron’s response to injury both contributes to strategies to improve functional axon regeneration after injury and adds to our understanding of the mechanisms that regulate post-developmental axon growth and synapse formation.