FGF-2 CONVERTS MATURE OLIGODENDROCYTES TO A NOVEL PHENOTYPE

Fibroblast growth factor (FGF)-2 differentially regulates oligodendroc yte progenitor proliferation and differentiation in culture, and modul ates gene expression of its own receptors, in a developmental and rece ptor type-specific manner (Bansal et al., 1996a,b). Three FGF receptor s (types 1, 2, 3) are expressed in postmitotic, terminally differentia ting oligodendrocytes, Exposure of such cells to FGF-2 results in: (a) the down-regulation of myelin-specific gene expression (e.g., ceramid e galactosyltransferase, 2',3'-cyclic nucleotide 3'-phosphohydrolase, myelin basic protein, proteolipid protein), (b) dramatic increases in the length of cellular processes in a time-and dose-dependent manner, (c) re-entrance into the cell cycle without accompanying mitosis, and (d) the alteration of the expression of both low-and high-affinity FGF receptors. Compared to oligodendrocyte progenitors, the differentiate d oligodendrocytes treated with FGF-2 incorporate BrdU at a slower rat es, exhibit different patterns of both FGF high-and low-affinity (synd ecans) receptors, and are morphologically very different, In addition, they do not re-express the progenitor markers A2B5, NG2 or PDGF alpha receptor, Therefore, although the FGF-treated cells lose their differ entiated OL/myelin markers, they do not revert to progenitors and clea rly represent a different, apparently novel, phenotype both morphologi cally and biochemically, which we have termed NOLs. These data indicat e-that terminally differentiated oligodendrocytes retain the plasticit y to reprogram their differentiation fate under the influence of envir onmental factors, The possible significance of this response to FGF re lative to normal and pathological physiology is discussed, In particul ar, on the basis of these data we predict the appearance of cells in a nd around multiple sclerosis plaques with the phenotype O4(+), NG2(-), A2B5(-), O1(-), MBP-. (C) 1997 Wiley-Liss, Inc.