Dock1 functions in Schwann cells to regulate development, maintenance, and repair

Schwann cells, the myelinating glia of the peripheral nervous system (PNS), are critical for myelin development, maintenance, and repair. Rac1 is a known regulator of radial sorting, a key step in developmental myelination. Previously, in zebrafish, we showed that the loss of Dock1, a Rac1-specific guanine nucleotide exchange factor, resulted in delayed peripheral myelination during development. Here, we demonstrate that Dock1 is necessary for myelin maintenance and remyelination after injury in adult zebrafish. Furthermore, Dock1 performs an evolutionarily conserved role in mice, functioning cell autonomously in Schwann cells to regulate the development, maintenance, and repair of peripheral myelin. Pharmacological and genetic manipulation of Rac1 in larval zebrafish, along with the analysis of active Rac1 levels in developing Dock1 mutant mouse nerves, revealed an interaction between these two proteins. We propose that the interplay between Dock1 and Rac1 signaling in Schwann cells is required to establish, maintain, and facilitate repair and remyelination within the PNS.