Basic fibroblast growth factor increases division and delays differentiation of dopamine precursors in vitro

Abstract

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 clay 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.