Functional neuronal circuits are subject to environmental stress and mechanical injury during the normal life of an individual. However, the cellular mechanisms that repair neuronal damage after injury remain unclear. C. elegans offers tremendous advantages to address these questions. First genetic techniques are powerful in C. elegans, and their transparent body allows researchers to sever neuronal processes in adulthood using laser.
Using imaging, genetics and pharmacology, I found that in response to laser injury C. elegans neurons use conserved Ca2+/cAMP cascade. The effect of Ca2+ or cAMP in axon regrowth is dependent on the p38 MAP Kinase pathway involving Dual Leucine Zipper Kinase (DLK-1), which is recently discovered as a determinant of axon regeneration. . Thus, the DLK-1 MAPK cascade could be one of the outputs of Ca2+/cAMP signaling that links injury response to repair pathways.
Genetic screening and in vivo imaging further revealed that one of the key targets of the DLK-1 MAPK pathway is axonal microtubule cytoskeleton. Specifically, I found that the DLK-1 cascade negatively regulates kinesin-13 (a kinesin which depolymerizes microtubule) and promotes post-translation modification of ?-tubulin to convert the stabilized axonal cytoskeleton to a dynamically growing cytoskeleton. This study revealed an axonal plasticity mechanism that is triggered by axonal injury. This also stimulated new research questions in nervous system repair in the context of neuronal network