While trophic support from targets depends on innervation, recent evid
ence suggests that local VIP promotes survival of sympathetic neurobla
sts prior to target interactions, during the period of neurogenesis. D
evelopmental studies now indicate that VIP expression peaks at embyron
ic day 15.5 (E15.5) in sympathetic ganglia in vivo, decreasing 3-fold
by birth. The expression pattern in vivo paralleled the time course of
ganglion neuroblast mitosis and peptide promotion of survival in cult
ure. In contrast, nerve growth factor (NGF) exhibited a reciprocal tro
phic relationship, primarily supporting older neurons that were unresp
onsive to VIP. To define relationships of trophism to mitosis, serial
time-lapse photography was employed to document the fate of neuroblast
s produced by cytokinesis in vitro. In the absence of trophic factors,
up to 80% of newly born cells died by 48 h, while virtually all neuro
blasts survived in response to VIP plus NGF. In addition, trophic fact
ors elicited multiple rounds of precursor division and an increase in
absolute cell number, indicating that both trophic and mitogenic mecha
nisms contribute to proliferation. In aggregate, these observations su
ggest that VIP is expressed locally during a critical fetal period, pr
oviding trophic support to dividing ganglion neuroblasts prior to the
action of target-derived NGF.