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The Journal of Neuroscience, August 15, 1999, 19(16):7077-7088
Multiple Roles of Bone Morphogenetic Protein Signaling in the
Regulation of Cortical Cell Number and Phenotype
Peter C.
Mabie,
Mark F.
Mehler, and
John 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
Members of the bone morphogenetic protein (BMP) family have been
implicated in multiple aspects of neural development in both the
CNS and peripheral nervous system. BMP ligands and receptors, as
well as the BMP antagonist noggin, are expressed in the developing cerebral cortex, making the BMPs likely candidates for regulating cortical development. To define the role of these factors in the developing cerebral cortex, we examined the effects of BMP2 and BMP4 on
cortical cells in vitro. Cells were cultured from
embryonic day 13 (E13) and E16 rat cerebral cortex in the absence or
presence of different concentrations of fibroblast growth factor 2, a
known regulator of cortical cell proliferation and differentiation. At
E13, the BMPs promoted cell death and inhibited proliferation of
cortical ventricular zone cells, resulting in the generation of fewer
neurons and no glia. At E16, the effects of the BMPs were more complex.
Concentrations of BMP2 in the range of 1-10 ng/ml promoted neuronal
and astroglial differentiation and inhibited oligodendroglial
differentiation, whereas 100 ng/ml BMP2 promoted cell death and
inhibited proliferation. Addition of the BMP antagonist noggin promoted
oligodendrogliogenesis in vitro, demonstrating that
endogenous BMP signaling influences the differentiation of cortical
cells in vitro. The distribution of BMP2 and noggin
within the developing cortex suggests that local concentrations of
ligands and antagonists define gradients of BMP signaling during
corticogenesis. Together, these results support the hypothesis that the
BMPs and their antagonist noggin co-regulate cortical cell fate and morphogenesis.
Key words:
bone morphogenetic protein; embryogenesis; fibroblast
growth factor; gliogenesis; neurogenesis; noggin; subventricular zone; ventricular zone
Copyright © 1999 Society for Neuroscience 0270-6474/99/19167077-12$05.00/0
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