Intrinsic mechanisms for axon regeneration: insights from injured axons in Drosophila

Axonal damage and loss are common and negative consequences of neuronal injuries, and also occur in some neurodegenerative diseases. For neurons to have a chance to repair their connections, they need to survive the damage, initiate new axonal growth, and ultimately establish new synaptic connections. This review discusses how recent work in Drosophila models have informed our understanding of the cellular pathways used by neurons to respond to axonal injuries. Similarly to mammalian neurons, Drosophila neurons appear to be more limited in their capacity regrow (regenerate) damaged axons in the central nervous system, but can undergo axonal regeneration to varying extents in the peripheral nervous system. Conserved cellular pathways are activated by axonal injury via mechanisms that are specific to axons but not dendrites, and new unanticipated inhibitors of axon regeneration can be identified via genetic screening. These findings, made predominantly via genetic and live imaging methods in Drosophila, emphasize the utility of this model organism for the identification and study of basic cellular mechanisms used for neuronal repair.