FIBROBLAST GROWTH-FACTOR DIFFERENTIALLY MODULATES THE NEUROTRANSMITTER PHENOTYPE OF CULTURED SYMPATHETIC NEURONS

Fibroblast growth factors (FGFs) are multifunctional growth factors that increase the proliferation of mesoderm- and neuroectoderm-derived cells and promote neuronal survival and neurite outgrowth in various regions of the brain, yet the physiological role(s) they may play in nervous system function and/or development is unclear. The present report demonstrates, using a well-characterized system, avian sympathetic neurons in vitro, that acidic and basic FGFs increase ChAT but decrease tyrosine hydroxylase (TH) activity in these cells, without affecting neuronal growth and survival. Heparin, which binds to FGFs with a high affinity, potentiates the activity of FGF on ChAT, but not TH. The time course of FGF action on the neurotransmitter phenotype is slow since effects start to appear after 1-2 d only. FGFs may thus modulate the activities of ChAT and TH by differentially regulating the expression of the genes coding for these enzymes. In conclusion, this report provides evidence supporting the hypothesis that FGFs may play a role in regulating neurotransmitter expression in sympathetic neurons during development independently of any effect on neuronal survival.