GGF/neuregulin induces a phenotypic reversion of oligodendrocytes

We have previously shown that glial growth factor (GGF), a member of the ne uregulin (NRG) family of growth factors, isa mitogen and survival factor fo r oligodendrocyte progenitors in cell culture and blocks their differentiat ion at the pro-oligodendrocyte stage (P. D. Canoll et al., 1996, Neuron 17, 229-243). We now show that GGF is able to induce differentiated oligodendr ocytes to undergo a phenotypic reversion characterized by loss of MBP expre ssion, reexpression of the intermediate filament protein nestin, reorganiza tion of the actin cytoskeleton, and a dramatic reduction in the number of p rocesses per cell. TUNEL analysis demonstrates that GGF is not cytotoxic fo r mature oligodendrocytes, but rather enhances their survival. GGF also ind uces the rapid activation of the PI 3-kinase and MAP kinase signaling pathw ays. These results further support a role for the NRGs in promoting the pro liferation and survival of and inhibiting the differentiation of cells in t he oligodendrocyte lineage and demonstrate that oligodendrocytes that diffe rentiate in culture retain a substantial degree of phenotypic plasticity.