The Rules of Attraction in Central Nervous System Myelination

Abstract

The wrapping of myelin around axons is crucial for the development and function of the central nervous system (CNS) of vertebrates, greatly regulating the conduction of action potentials. Oligodendrocytes, the myelinating glia of the CNS, have an intrinsic tendency to wrap myelin around any permissive structure in vitro, but in vivo, myelin is targeted with remarkable specificity only to certain axons. Despite the importance of myelination, the mechanisms by which oligodendrocytes navigate a complex milieu that includes many types of cells and their cellular projections and select only certain axons for myelination remains incompletely understood. In this Mini-review, I highlight recent studies that shed light on the molecular and cellular rules governing CNS myelin targeting.

Keywords: attraction; axon-glia interactions; myelin; oligodendrocyte; targeting.

FIGURE 1

Regulation of CNS myelin targeting. (A) myelin is targeted in a short period in the life of an oligodendrocyte (OL): a selection stage during differentiation and a refinement stage after differentiation. (B) Biophysical properties of diameter and/or curvature determine the permissiveness of a target for myelination. (C) Curvature or length-sensing proteins in oligodendrocyte processes may sense appropriately sized targets. (D) Attractive and repulsive cell-adhesion molecules on prospective targets regulating CNS myelination. (E) Similar to synapse formation, the temporal dynamics of key signaling pathways (e.g., Eph) may determine the fate of OPC processes during myelin target selection.