SUMMARY
Oligodendrocyte precursor cells (OPCs) give rise to both oligodendrocytes, the myelinating cell type of the central nervous system, and NG2 glia, which are the most proliferative cells in the adult mammalian brain. NG2 glia retain characteristics of OPCs, and some NG2 glia produce oligodendrocytes, but many others persist as NG2 glia throughout adulthood. Why some OPCs differentiate as oligodendrocytes whereas others become NG2 glia is not known. Using zebrafish spinal cord as a model, we found that oligodendrocytes and NG2 glia arise in sequential waves from distinct neural progenitors. Additionally, oligodendrocyte and NG2 cell fates are specified during a defined critical period by small differences in Shh signaling and Notch activity, which modulates Shh signaling response. Thus, our data indicate that OPCs fated to produce oligodendrocytes and NG2 glia are specified as distinct cell types, raising the possibility that the myelinating potential of OPCs is set by graded Shh signaling activity.