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Volume 17, Number 11,
Issue of June 1, 1997
pp. 4112-4120
Copyright ©1997 Society for Neuroscience
Bone Morphogenetic Proteins Induce Astroglial Differentiation of
Oligodendroglial-Astroglial Progenitor Cells
Received Sept. 4, 1996; revised Feb. 3, 1997; accepted March 24, 1997.
P. C. Mabie,
M. F. Mehler,
R. Marmur,
A. Papavasiliou,
Q. Song, and
J. A. Kessler
Departments of Neurology and Neuroscience and the R. F. Kennedy
Center for Research in Mental Retardation and Human Development, Albert
Einstein College of Medicine, Bronx, New York 10461
We have used bipotent postnatal cortical
oligodendroglial-astroglial progenitor cells (O-2As) to examine the
role of inductive signals in astroglial 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 subclass of the transforming
growth factor  (TGF) superfamily, promote the selective,
dose-dependent differentiation of O-2As into astrocytes with concurrent
suppression of oligodendroglial differentiation. This
astroglial-inductive action is not sanctioned by other members of the
TGF superfamily. Astroglial differentiation requires only very brief
initial exposure to the BMPs and is accompanied by increased cellular
survival and accelerated exit from cell cycle. Dual-label
immunofluorescence microscopy documents that O-2A progenitor cells
express a complement of BMP type I and type II receptor subunits
required for signal transduction. Furthermore, expression of BMP2
in vivo reaches maximal levels during the period of
gliogenesis. These results suggest that the BMPs act as potent inductive factors in postnatal glial lineage commitment that initiate a
stable program of astroglial differentiation.
Key words:
astrocyte;
bone morphogenetic protein;
lineage
commitment;
oligodendrocyte-astrocyte type 2 progenitor;
transforming
growth factor superfamily;
central nervous system development
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