VASOACTIVE-INTESTINAL-PEPTIDE SHORTENS BOTH G1 AND S-PHASE OF NEURAL CELL-CYCLE IN WHOLE POSTIMPLANTATION CULTURED MOUSE EMBRYOS

Vasoactive intestinal peptide, a trophic and mitogenic factor, stimula tes growth in whole cultured mouse embryos. Inhibition of this growth function between embryonic days 9 and 11 induces growth retardation ac companied by severe microcephaly. In the present study, to determine t he effects of this peptide on the different phases of the cell cycle o f neural cells, embryonic day 9.5 cultured mouse embryos were cumulati vely labelled with bromodeoxyuridine. Vasoactive intestinal peptide (1 0(-7)M) shortened S phase and G1 phase of neuroepithelial cells by 50% (4.8-2.4 h) and 58% (1.9-0.8 h), respectively, compared with controls . G2 and M phases were not modified by vasoactive intestinal peptide t reatment. Total cell cycle length was consequently reduced by 43% (8.2 -4.7 h) in vasoactive intestinal peptide treated embryos, compared wit h controls. In contrast, vasoactive intestinal peptide did not modify the rate of neuroepithelial cell death as assessed by the proportion o f nuclei containing fragmented DNA. These data suggest that vasoactive intestinal peptide stimulates growth in premigratory stages of nervou s system development by shortening S and G1 phases of the cell cycle a nd that S phase duration can be regulated by a physiological peptide.