From neural stem cells to myelinating oligodendrocytes

The potential to generate oligodendrocytes progenitors (OP) from neural ste m 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 pote nt regulators of early and late OP development. The ability to isolate and grow NSCs as well as glial-restricted progenitors has revealed that FGF2 an d thyroid hormone favor an oligodendrocyte fate. Analysis of genetically mo dified mice showed that PDGF controls the migration and production of oligo dendrocytes in vivo. Interplay between mitogens, thyroid hormone, and neuro transmitters 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 precursor s, rather than slowly cycling OF, appear the cells of choice to rapidly gen erate myelin-forming cells.