Vasoactive intestinal peptide shortens both G1 and S phases of neural cell cycle in whole postimplantation cultured mouse embryos.
Vasoactive intestinal peptide, a trophic and mitogenic factor, stimulates growth in whole cultured mouse embryos. Inhibition of this growth function between embryonic days 9 and 11 induces growth retardation accompanied by severe microcephaly. In the present study, to determine the effects of this peptide on the different phases of the cell cycle of neural cells, embryonic day 9.5 cultured mouse embryos were cumulatively labelled with bromodeoxyuridine. Vasoactive intestinal peptide (10(-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 treatment. Total cell cycle length was consequently reduced by 43% (8.2-4.7 h) in vasoactive intestinal peptide treated embryos, compared with controls. In contrast, vasoactive intestinal peptide did not modify the rate of neuroepithelial cell death as assessed by the proportion of nuclei containing fragmented DNA. These data suggest that vasoactive intestinal peptide stimulates growth in premigratory stages of nervous system development by shortening S and G1 phases of the cell cycle and that S phase duration can be regulated by a physiological peptide.
Gressens
P
P
Service de Neuropédiatrie and INSERM CRI 97-01, Hôpital Robert-Debré and Faculté Xavier Bichat, Paris, France. pierre.gressens@rdb.ap-hop-paris.fr
Paindaveine
B
B
Hill
J M
JM
Evrard
P
P
Brenneman
D E
DE
D000818:Animals; D046508:Culture Techniques; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects*; D047108:Embryonic Development; D005314:Embryonic and Fetal Development / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D016193:G1 Phase / Q000187:drug effects*; D051379:Mice; D009420:Nervous System / Q000166:cytology / Q000187:drug effects* / Q000196:embryology; D011247:Pregnancy; D016196:S Phase / Q000187:drug effects*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D014660:Vasoactive Intestinal Peptide