Spinal cord precursors utilize neural crest cell mechanisms to generate hybrid peripheral myelinating glia.

During development, oligodendrocytes and Schwann cells myelinate central and peripheral nervous system axons, respectively, while motor exit point (MEP) glia are neural tube-derived, peripheral glia that myelinate axonal territory between these populations at MEP transition zones. From which specific neural tube precursors MEP glia are specified, and how they exit the neural tube to migrate onto peripheral motor axons, remain largely unknown. Here, using zebrafish, we found that MEP glia arise from lateral floor plate precursors and require foxd3 to delaminate and exit the spinal cord. Additionally, we show that similar to Schwann cells, MEP glial development depends on axonally derived neuregulin1. Finally, our data demonstrate that overexpressing axonal cues is sufficient to generate additional MEP glia in the spinal cord. Overall, these studies provide new insight into how a novel population of hybrid, peripheral myelinating glia are generated from neural tube precursors and migrate into the periphery.