TROPHIC MECHANISMS REGULATE MITOTIC NEURONAL PRECURSORS - ROLE OF VASOACTIVE-INTESTINAL-PEPTIDE (VIP)

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.