Golgi compaction facilitates microtubule nucleation to drive adult vertebrate peripheral neuron regeneration

Peripheral neurons regenerate in response to injury, but their cell intrinsic processes are poorly understood and seldom sufficient to effect clinical restoration. Using a novel assay for high-resolution live imaging of regenerating adult vertebrate neurons, we identify acute fragmentation and rapid recompaction of the somatic Golgi as a key driver of peripheral neuron regeneration, implicating this organelle as a therapeutic target in an area of clinical unmet need. Compaction of the fragmented Golgi facilitates stepwise recruitment of the microtubule nucleation factors AKAP9 and γ-tubulin within a discrete period that corresponds with acentrosomal Golgi-mediated microtubule nucleation. Furthermore, disruption of AKAP9 or γ-tubulin recruitment compromises microtubule nucleation leading to impaired regeneration. Crucially, these mechanisms are conserved in the contexts of in vivo rat sciatic nerve transection and in primary human peripheral neurons. This work transforms our understanding of the cell intrinsic mechanisms that render injured peripheral neurons competent to initiate axon regeneration.