How do neurons recognize that they have been injured? What mechanisms link injury to the initiation of growth?
We discovered that the dual-leucine zipper MAP3K DLK-1 is a critical link between axon damage and initiation of regeneration.
We are studying mechanisms downstream of DLK signals that mediate regeneration. We discovered that DLK controls transcription of two enzymes that affect poly(ADP-ribosylation), and that PAR levels help determine the regeneration competence of neurons in C. elegans and cultured mouse neurons.
Our genetic screens identified many additional molecules that affect regeneration. We showed that two key signaling modalities--Notch signaling and syndecan--control axon regeneration by acting in neurons.
Overall our goal is to understand how neurons use intracellular signaling pathways to interpret information about axon damage and control axon regeneration.