NT-3 STIMULATES SYMPATHETIC NEUROBLAST PROLIFERATION BY PROMOTING PRECURSOR SURVIVAL

Although proliferation is fundamental to the generation of neuronal po pulations, little is known about the function of trophic mechanisms du ring neurogenesis. We now describe a novel role for neurotrophin-3 (NT -3): the neurotrophin stimulates proliferation of sympathetic neurobla sts through trophic mechanisms. NT-3 promotes survival of the dividing precursors, but does not directly stimulate mitosis. NT-3 trophic eff ects differ markedly from those of the sympathetic mitogen, insulin. F urthermore, whereas NT-3 exhibits trophic activity for dividing neurob lasts, nerve growth factor characteristically promotes survival of pos tnatal sympathetic neurons. The stage-specific activity of NT-3 and ne rve growth factor in culture parallels the sequence of trkC and trkA r eceptor gene expression detected in vivo. Thus, neurotrophins apparent ly serve as trophic factors during ontogeny, acting sequentially durin g establishment of individual populations.