Mitogenic effect of basic fibroblast growth factor on embryonic ventral mesencephalic dopaminergic neurone precursors

The effects of embryonic age and the presence of basic fibroblast growth factor (bFGF) have been examined on the survival and rate of cell division of dopaminergic neurones of the ventral mesencephalon. Cultures were produced from 7.5 mm and 11 mm rat embryos, pulsed with [3H]thymidine during the first 12 h, and the survival and labelling of cells measured after 3 and 7 days in vitro. bFGF largely prevented the decline in numbers of tyrosine hydroxylase (TH)-positive neurones that occurred in control cultures between 3 days and 1 week. In cultures derived from the younger 7.5 mm embryos there were more TH-positive neurones in the presence of exogenous bFGF than under control conditions after 3 days in vitro. No similar effect was seen in the cultures derived from the older 11 mm embryos. Combined [3H]thymidine labelling and TH immunocytochemistry suggested that this effect was attributable, at least in part, to a bFGF-associated increase in the proliferation of TH-positive neurone progenitors during the first day or so, which was seen in cultures from 7.5 mm but not 11 mm embryos. The effect of bFGF on cultures from older embryos is therefore purely on neuronal survival, while the effect on cultures from younger embryos is a mixture of survival and mitogenic actions.