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.