Mechanisms regulating the development of oligodendrocytes and central nervous system myelin

Abstract

Oligodendrocytes and the myelin they produce are a remarkable vertebrate specialization that enables rapid and efficient nerve conduction within the central nervous system. The generation of myelin during development involves a finely-tuned pathway of oligodendrocyte precursor specification, proliferation and migration followed by differentiation and the subsequent myelination of appropriate axons. In this review we summarize the molecular mechanisms known to regulate each of these processes, including the extracellular ligands that promote or inhibit development of the oligodendrocyte lineage, the intracellular pathways they signal through and the key transcription factors that mediate their effects. Many of these regulatory mechanisms have recurring roles in regulating several transitions during oligodendrocyte development, highlighting their importance. It is also highly likely that many of these developmental mechanisms will also be involved in myelin repair in human neurological disease.

Mutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features

“…A minority of patients have shown a reduced white matter volume on brain MRI [participant MI1003; SI Appendix, Table S1; and also an affected individual in the study by Celis et al (14)]. Interestingly, in mouse, we observe strong Gpt2 expression in oligodendrocyte precursor cells that undergo rapid expansion in the early postnatal period (19,(27)(28)(29).…”

“…S4B). Based on these data, peak levels of GPT2 expression correlate with major periods of synaptogenesis and myelination in both mouse and human developing postnatal brain (16)(17)(18)(19).…”

Myelination at a glance

“…To make this adjustment, neurons have to control signalling pathways that drive myelination in oligodendrocytes. An in-depth discussion of these signals is beyond our scope but we will briefly consider them in the context of myelin growth and wrapping (for a more detailed review, see Mitew et al, 2013;Piaton et al, 2010;Taveggia et al, 2010;Simons and Lyons, 2013;Fancy et al, 2011;White and Krämer-Albers, 2014). To generate myelin, the distinct but interconnected processes of compaction and radial and longitudinal growth need to be tightly coordinated.…”

A Modular Assembly of Spinal Cord–Like Tissue Allows Targeted Tissue Repair in the Transected Spinal Cord

“…When the SCLT was assembled, remarkably, multilayered myelin sheath was observed with axon being enwrapped in the WMLT region. Indeed, the delicate balance between the inhibitory and promoting molecules derived from axon is believed to be essential to guide the thickness of the myelin sheath 26. Meanwhile, the oligodendrocyte offers a variety of trophic factors that help the development and survival of neuron 27.…”