Rnd2 Uniquely Regulates Myelination by Oligodendrocytes Depending on Myelinating Process

Abstract

Oligodendrocyte precursor cells differentiate into oligodendrocytes to wrap their plasma membranes around axons. While myelination is known to be one of the most dynamic cell morphological changes, the overall molecular pictures remain to be elucidated. Herein we describe the biphasic roles of Rnd2, an atypical branch of the Rho GTPase, in oligodendrocyte myelination during development and after maturation. Oligodendrocyte-specific Rnd2 knockout mice exhibit decreased myelin thickness in the onset of myelination whereas the knockout increased thickness in the subsequent process. Consistently, the biphasic role of Rnd2 is obtained using oligodendrocyte-specific Rnd2 transgenic mice. Indeed, Rho kinase and the substrate Mbs, the signaling unit regulating negatively myelination, exist in the decreased phosphorylated forms in the early developmental stage and in the increased phosphorylated forms in the subsequent stage. Therefore, Rnd2 uniquely regulates myelination, demonstrating the presence of a modulator that plays different roles depending on the myelination process.

Keywords: myelination; oligodendrocyte; biphasic; Rnd2; knockout; transgenic