From neural stem cells to myelinating oligodendrocytes.

The potential to generate oligodendrocytes progenitors (OP) from neural stem cells (NSCs) exists throughout the developing CNS. Yet, in the embryonic spinal cord, the oligodendrocyte phenotype is induced by sonic hedgehog in a restricted anterior region. In addition, neuregulins are emerging as potent regulators of early and late OP development. The ability to isolate and grow NSCs as well as glial-restricted progenitors has revealed that FGF2 and thyroid hormone favor an oligodendrocyte fate. Analysis of genetically modified mice showed that PDGF controls the migration and production of oligodendrocytes in vivo. Interplay between mitogens, thyroid hormone, and neurotransmitters may maintain the undifferentiated stage or result in OP growth arrest. Notch signaling by axons inhibits oligodendrocyte differentiation until neuronal signals--linked to electrical activity-trigger initiation of myelination. To repair myelin in adult CNS, multipotential neural precursors, rather than slowly cycling OP, appear the cells of choice to rapidly generate myelin-forming cells.