Growth factor function of vasoactive intestinal peptide in whole cultured mouse embryos

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Abstract
FACTORS controlling central nervous system (CNS) growth immediately after neurulation are mostly unknown. Vasoactive intestinal peptide (VIP) receptors are widely distributed in the embryonic nervous system1,2, and VIP has trophic and mitogenic properties3,4 on embryonic neural tissues but inhibits growth5 and mitosis in certain tumours6. To address the potential effects of VIP on embryonic growth, we used whole postimplantation embryo cultures7,8. After a 4-h incubation, VIP stimulated growth, increasing somite number, embryonic volume, DNA and protein content, and number of cells in S-phase. A VIP antagonist9,10 substantially inhibited these VIP-mediated increments in growth. The VIP antagonist completely suppressed VIP-stimulated mitosis in the CNS while decreasing the same in non-neuronal tissues by 38%. In vitro autoradiography revealed GTP-sensitive and GTP-insensitive VIP receptors which were differentially regulated in VIP antagonist-treated embryos. The present study suggests that VIP acts as a growth factor on early postimplantation embryos through multiple VIP receptors that exhibit tissue-specific responses.