Dock1 acts cell-autonomously in Schwann cells to regulate the development, maintenance, and repair of peripheral myelin

Abstract

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, and we previously showed in zebrafish that loss of Dock1, a Rac1-specific guanine nucleotide exchange factor, results in delayed peripheral myelination in development. We demonstrate here that Dock1 is necessary for myelin maintenance and remyelination after injury in adult zebrafish. Furthermore, it performs an evolutionary conserved role in mice, acting cell-autonomously in Schwann cells to regulate peripheral myelin development, maintenance, and repair. Additionally, manipulating Rac1 levels in larval zebrafish reveals thatdock1mutants are sensitized to inhibition of Rac1, suggesting an interaction between the two proteins during PNS development. 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 peripheral nervous system.