miRNAs As Emerging Regulators of Oligodendrocyte Development and Differentiation

Dylan A. Galloway, Craig S. Moore

Chronic demyelination is a hallmark of neurological disorders such as multiple sclerosis (MS) and several leukodystrophies. In the central nervous system (CNS), remyelination is a regenerative process that is often inadequate during these pathological states. In the MS context, in situ evidence suggests that remyelination is mediated by populations of oligodendrocyte progenitor cells (OPCs) that proliferate, migrate, and differentiate into mature, myelin-producing oligodendrocytes at sites of demyelinated lesions. The molecular programming of OPCs into mature oligodendrocytes is governed by a myriad of complex intracellular signaling pathways that modulate this process. Recent research has demonstrated the importance of specific and short non-coding RNAs, known as microRNAs (miRNAs), in regulating OPC differentiation and remyelination. Fortunately, it may be possible to take advantage of numerous developmental studies (both human and rodent) that have previously characterized miRNA expression profiles from the early neural progenitor cell to the late myelin-producing oligodendrocyte. Here we review much of the work to date and discuss the impact of miRNAs on OPC and oligodendrocyte biology. Additionally, we consider the potential for miRNA-mediated therapy in the context of remyelination and brain repair.