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Journal of Neuroscience, Vol 15, 7141-7149, Copyright © 1995 by Society for Neuroscience
Basic fibroblast growth factor increases division and delays differentiation of dopamine precursors in vitro
MM Bouvier and C Mytilineou
Department of Neurology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Growth factors have been shown to be involved in the regulation of division
and differentiation of neuroepithelial cells. In the present study we
examined the ability of various factors to influence the development of
dopamine precursors. Primary neuronal cultures were prepared from the
embryonic day 12 (E12) rat ventral mesencephalon, a time and place which
coincides with the beginning of the birth of the dopamine neurons of the
substantia nigra pars compacta. At low plating density in serum-free
medium, the dopamine precursors divide for approximately 1 d in vitro. We
report here that basic fibroblast growth factor (bFGF) can expand the
period of dopamine precursor division at least until day 8 in culture,
which is well beyond the normal division of these cells. This increase in
cell division was accompanied by a delay in differentiation as compared to
untreated control cultures. Upon differentiation, the high-affinity
dopamine uptake values in bFGF- treated cultures were 20 times maximal
control values. Mature dopamine neurons appeared at the same time as
astrocytes, which may be playing a role in inducing dopamine neuron
differentiation. IGF-I, GDNF, and EGF were unable to mimic the effect of
bFGF on division and differentiation of dopamine precursors. Expanding in
vitro the number of dopamine precursors provides tissue that may be
suitable for transplantation in patients with Parkinson's disease.
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