NT-3 STIMULATES SYMPATHETIC NEUROBLAST PROLIFERATION BY PROMOTING PRECURSOR SURVIVAL

Although proliferation is fundamental to the generation of neuronal populations, little is known about the function of trophic mechanisms during neurogenesis. We now describe a novel role for neurotrophin-3 (NT-3): the neurotrophin stimulates proliferation of sympathetic neuroblasts through trophic mechanisms. NT-3 promotes survival of the dividing precursors, but does not directly stimulate mitosis. NT-3 trophic effects differ markedly from those of the sympathetic mitogen, insulin. Furthermore, whereas NT-3 exhibits trophic activity for dividing neuroblasts, nerve growth factor characteristically promotes survival of postnatal sympathetic neurons. The stage-specific activity of NT-3 and nerve growth factor in culture parallels the sequence of trkC and trkA receptor gene expression detected in vivo. Thus, neurotrophins apparently serve as trophic factors during ontogeny, acting sequentially during establishment of individual populations.