Rapid conduction of action potentials along motor axons requires that oligodendrocytes and Schwann cells myelinate distinct central and peripheral nervous system (CNS and PNS) domains along the same axon. Despite the importance of this arrangement for nervous system function, the mechanisms that establish and maintain this precise glial segregation at the motor exit point (MEP) transition zone are unknown. Using in vivo time-lapse imaging in zebrafish, we observed that prior to myelination, oligodendrocyte progenitor cells (OPCs) extend processes into the periphery via the MEP and immediately upon contact with spinal motor root glia retract back into the spinal cord. Characterization of the peripheral cell responsible for repelling OPC processes revealed that it was a novel, CNS-derived population of glia we propose calling MEP glia. Ablation of MEP glia resulted in the absence of myelinating glia along spinal motor root axons and an immediate breach of the MEP by OPCs. Taken together, our results identify a novel population of CNS-derived peripheral glia located at the MEP that selectively restrict the migration of OPCs into the periphery via contact-mediated inhibition.
The nervous system is often thought as two distinct halves: the central nervous system (CNS), which consists of the brain and spinal cord, and the peripheral nervous system (PNS), which includes the nerves that control movement and sense the environment. The cells within these two halves, however, do not commonly mix. To address how cells are segregated within these two compartments of the nervous system, we used live, transgenic zebrafish embryos to watch nerve development. Our study shows that CNS-residing myelinating glia (nonneuronal cells that wrap around nerves to ensure nerve impulse conduction) are restricted from entering the PNS by a cell we call motor exit point (MEP) glia. MEP glia originate from within the CNS, and then migrate into the PNS, divide, and produce cells that ensheath and myelinate spinal motor root axons. Ablation of MEP glia causes CNS glia to migrate inappropriately into the PNS, disrupting the normal boundary that is present between the CNS and PNS. Overall, the identification and characterization of MEP glia identifies an aspect of peripheral nerve composition that may be pertinent in human health and disease.