Cell cycle arrest induced by ectopic expression of p27 is not sufficient to promote oligodendrocyte differentiation

Oligodendrocyte differentiation is-accompanied by dramatic changes in gene expression as well as cell cycle arrest. To determine whether cell cycle ar rest is sufficient to induce the changes:in cell phenotype associated with differentiation, we inhibited oligodendrocyte precursor proliferation in vi tro by overexpressing p27, a cyclin kinase inhibitor, using a recombinant a denovirus. Ectopic expression of p27 efficiently inhibited oligodendrocyte precursor cell division, even in the presence of exogenous mitogens, by blo cking the activity of the cyclin-dependent kinase, cdk2. Although the cells had stopped dividing, they did not express galactocerebroside (GalC) or my elin: basic protein (MBP), changes associated with oligodendrocyte differen tiation, suggesting that they had not differentiated. After removal of exog enous mitogens, however, adenovirus-expressing oligodendrocyte precursors d ifferentiated with atemporal profile similar to that of control, uninfected oligodendrocytes, as indicated by expression of GalC and MBP. We conclude that cell cycle arrest is not sufficient to induce differentiation of divid ing oligodendrocyte precursors, and that modulation of additional, as yet u nknown, signaling pathways is required for this to occur. (C) 1999 Wiley-Li ss, Inc.