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The Journal of Neuroscience, May 15, 2001, 21(10):3483-3491
Immature Neurons From CNS Stem Cells Proliferate in Response to
Platelet-Derived Growth Factor
Anna
Erlandsson,
Maria
Enarsson, and
Karin
Forsberg-Nilsson
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala
University, SE-751 85 Uppsala, Sweden
Identifying external signals involved in the regulation of neural
stem cell proliferation and differentiation is fundamental to the
understanding of CNS development. In this study we show that
platelet-derived growth factor (PDGF) can act as a mitogen for neural
precursor cells. Multipotent stem cells from developing CNS can be
maintained in a proliferative state under serum-free conditions in the
presence of fibroblast growth factor-2 (FGF2) and induced to
differentiate into neurons, astrocytes, and oligodendrocytes on
withdrawal of the mitogen. PDGF has been suggested to play a role
during the differentiation into neurons. We have investigated the
effect of PDGF on cultured stem cells from embryonic rat cortex. The
PDGF -receptor is constantly expressed during differentiation of
neural stem cells but is phosphorylated only after PDGF-AA treatment. In contrast, the PDGF -receptor is hardly detectable in
uncommitted cells, but its expression increases during differentiation. We show that PDGF stimulation leads to c-fos induction,
5'-bromo-2'deoxyuridine incorporation, and an increase in the number of
immature cells stained with antibodies to neuronal markers. Our
findings suggest that PDGF acts as a mitogen in the early phase of stem
cell differentiation to expand the pool of immature neurons.
Key words:
PDGF; neural stem cells; differentiation; neurogenesis; rat; cortex; development
Copyright © 2001 Society for Neuroscience 0270-6474/01/21103483-09$05.00/0
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