SCG10 is required for peripheral axon maintenance and regeneration in mice.

Abstract

Proper microtubule dynamics is critical for neuronal morphogenesis and functions, and its dysregulation results in neurological disorders and regeneration failure. Superior cervical ganglion-10 (SCG10, also known as Stathmin-2) is a well-known regulator of microtubule dynamics in neurons, but its functions in the peripheral nervous system (PNS) remain largely unknown. Here, we show that Scg10 knockout mice exhibit severely progressive motor and sensory dysfunctions with significant sciatic nerve myelination deficits and neuromuscular degeneration. Furthermore, increased microtubule stability, shown by a significant increase in tubulin acetylation and decrease in tubulin tyrosination, and decreased axonal transport occur in Scg10 knockout DRG neurons. Meanwhile, SCG10 depletion impairs axon regeneration in both injured mouse sciatic nerve and cultured DRG neurons following replating, and the impaired axon regeneration was found to be induced by a lack of SCG10-mediated microtubule dynamics in the neurons. Thus, our results highlight the importance of SCG10 in peripheral axon maintenance and regeneration.