EVIDENCE FOR AN IMPORTANT ROLE OF IGF-I AND IGF-II FOR THE EARLY DEVELOPMENT OF CHICK SYMPATHETIC NEURONS

The ability of immature neurons from chick lumbosacral sympathetic ganglia to proliferate in vitro was used to identify factors that affect neurogenesis. Under serum-free culture conditions, insulin-like growth factor I (IGF-I), IGF-II, or insulin caused an increase in the proportion of cells that incorporated [H-3]thymidine. In addition, IGFs also stimulated neurite outgrowth from these immature sympathetic neurons. IGF-I and IGF-II mRNA was found to be expressed in E7 sympathetic ganglia during the period of neurogenesis. IGF-I was detectable in fibroblasts, whereas IGF-II mRNA was expressed by neurons, glia, and fibroblasts. Elimination of endogenous IGFs by neutralizing antibodies resulted in a reduction of neuron proliferation and neuron number, whereas elevation of IGF levels by treatment with IGF-I increased sympathetic neuron proliferation in vivo. These findings suggest an important role of IGFs for the development of sympathetic neurons and imply a general role of IGFs in the control of neurogenesis and neurite outgrowth.