BONE MORPHOGENETIC PROTEINS INDUCE ASTROGLIAL DIFFERENTIATION OF OLIGODENDROGLIAL-ASTROGLIAL PROGENITOR CELLS

We have used bipotent postnatal cortical oligodendroglial-astroglial p rogenitor cells (O-2As) to examine the role of inductive signals in as troglial lineage commitment. O-2A progenitor cells undergo progressive oligodendroglial differentiation when cultured in serum-free medium, but differentiate into astrocytes in medium supplemented with FBS. We now report that the bone morphogenetic proteins (BMPs), a major subcla ss of the transforming growth factor beta (TGF beta) superfamily, prom ote the selective, dose-dependent differentiation of O-2As into astroc ytes with concurrent suppression of oligodendroglial differentiation, This astroglial-inductive action is not sanctioned by other members of the TGF beta superfamily, Astroglial differentiation requires only ve ry brief initial exposure to the BMPs and is accompanied by increased cellular survival and accelerated exit from cell cycle. Dual-label imm unofluorescence microscopy documents that O-2A progenitor cells expres s a complement of BMP type I and type II receptor subunits required fo r signal transduction, Furthermore, expression of BMP2 in vivo reaches maximal levels during the period of gliogenesis, These results sugges t that the BMPs act as potent inductive factors in postnatal glial lin eage commitment that initiate a stable program of astroglial different iation.