We have investigated the effect of basic fibroblast INTRODUCTION growth factor (bFGF) on the proliferation and phenotype of differentiated oligodendroglia. Using primary cell cultures enriched in oligodendrocytes but containing few 02A-oligodendrocyte progenitor cells, we demonstrate that bFGF treatment greatly increases the proportion of 02A cells while decreasing the proportion of galactocerebroside + (GalC +), myelin basic protein + (MBP+) oligodendrocytes, and the steady state levels of MPB mRNA. Complement mediated cell lysis experiments using the A2B5 antibody to deplete existing 02A cells or the R-Mab antibody to deplete existing oligodendroglia show that bFGF elicits a rapid increase in the number of 02A cells in cultures previously depleted of 0 2 A cells, but does not cause an early increase in 02A cells in cultures from which oligodendroglia had been removed, indicating that the oligodendrocytes are the source of the newly recruited 02A cells. This bFGF-mediated transition from oligodendrocyte to 02A cells occurs with a time course similar to the bFGF-induced increase of the proliferation rate of the GalC+ oligodendrocytes. Studies with purified, passaged cells of the oligodendroglial lineage show that bFGF augments oligodendroglial dedifferentiation and proliferation in chronologically adult oligodendrocytes and in the virtual absence of other cell types. We have thus demonstrated that mature oligodendrocytes are induced by bFGF to dedifferentiate and proliferate, suggesting a mechanism for regeneration of the oligodendroglial lineage following demyelinating During CNS development, oligodendrocyte precursor cells arise from the germinal matrix zone and migrate into the neighboring gray and white matter where they differentiate into oligodendrocytes and begin to synthesize myelin (Goldman ct al., 1986). The detailed events occurring during the differentiation of oligodendrocyte precursors have been studied in tissue culture using a series of specific antibodies which mark the stages in the oligodendrocyte lineage. Motile oligodendrocyte precursors, called 0 2 A cells, which have been detected both in vitro and in vivo, express surface glycolipids which can be recognized by the antibodies A2B5 (Eisenbarth et al., 1979) and GD3 (Goldman et al., 1986). In culture, 0 2 A cells divided up to 8 times before differentiating into oligodendrocytes (Temple and Raff, 1986;Raff, 1989). Oligodendrocytes are recognized by the anti-galactolipid antibody R-Mab (Ranscht et a]., 1982) and the antigalactocerebroside antibody, 0 1, (Sommer and Schachner, 198 l), which delineate slightly different stages of oligodendrocyte maturity (Bansal et al., 1989;Bansal and Pfeiffer, 1992). Oligodcndrocytes in culture also express the myelin proteins, myelin basic protein (MBP) and proteolipid protein (PLP).
Recent studies have shown that several brain-derived polypeptide growth factors contribute to the regulation of the development of the oligodendroglial lineage. Platelet derived growth factor (PDGF), secreted by both astrocytes (Richardson et a]. , 1988) and neurons (Sasahara et al., 1991;Yeh et al., 1991), acts as a surdisease.