Oligodendrocytes develop from neuroepithelial cells and myelinate axons in the CNS. Our understanding of their development is limited, since quantities sufficient for biochemical analyses cannot be purified and the stem cells from which they originate have not been isolated. To get around this problem,Nathalie Billon and co-workers have developed a method for generating oligodendrocytes in vitro (see ). They engineered ES cells to express drug-resistance/susceptibility genes from promoters active in neuroepithelial cells (βgeo-Sox2) and undifferentiated ES cells(tk-Oct4) and used the drugs (G418 and Ganciclovir) to select for neuroepithelial cells and eliminate undifferentiated ES cells, respectively;they then exposed the cells to signals known to promote oligodendrocyte differentiation (FGF-2, Sonic Hedgehog, PDGF-AA and thyroid hormone). Under these conditions, the cells followed the developmental pathway observed in vivo, adopting the correct morphology and expressing appropriate markers(Olig2, PDGFRα, NG2 proteoglycan and galactocerebroside) at the correct times. The technique indicates that an important developmental lineage can be reconstituted entirely from ES cells. Moreover, it could be adapted to produce human cells and thus be used in treatment of demyelinating diseases such as multiple sclerosis.
