Knocking out non-muscle myosin II in retinal ganglion cells promotes long-distance optic nerve regeneration (RNA-Seq II)

In addition to altered gene expression, pathological cytoskeletal dynamics in the axon are another key intrinsic barrier for axon regeneration in the central nervous system (CNS). Here we showed that knocking out myosin IIA/B in retinal ganglion cells alone either before or after optic nerve crush induced significant optic nerve regeneration. Combined Lin28a overexpression and myosin IIA/B knockout led to additive promoting effect and long-distance axon regeneration. Immunostaining, RNA sequencing and western blot analyses revealed that myosin II deletion did not affect known axon regeneration signaling pathways or the expression of regeneration associated genes. Instead, it abolished the retraction bulb formation and significantly enhanced the axon extension efficiency. The study provided clear evidence that directly targeting neuronal cytoskeleton was sufficient to induce significant CNS axon regeneration, and combining altered gene expression in the soma and modified cytoskeletal dynamics in the axon was a promising approach for long-distance CNS axon regeneration Lumbar 4 and 5 Dorsal root ganglia mRNA profiles of Myh9/10 double-floxed mice (WT) and Advillin-Cre:Myh9/10 double-floxed mice (dKO) 3 days following sham surgery or sciatic nerve axotomy were generated by RNA-seq in duplicate.