PACAP maintains cell cycling and inhibits apoptosis in chick neuroblasts.
We previously reported that pituitary adenylate cyclase-activating polypeptide (PACAP) increased cAMP in neuroblast-enriched cultures from embryonic day 3.5 chick brain. Also, the neuroblasts expressed the mRNA, peptide, and receptor for PACAP. Here, we investigated downstream effects of increased cAMP by examining PACAP's role in regulating cell numbers during brain development. Using flow cytometry, we quantified proliferating cell nuclear antigen and DNA, and compared apoptotic cells and cells in cell cycle compartments under differing conditions. Untreated cultures showed high proliferative activity with little apoptosis. Addition of exogenous PACAP had no effect on this pattern. However, blocking endogenous PACAP with a receptor antagonist increased cell cycle exit, then increased apoptosis. We conclude that chick neuroblasts require production of PACAP to inhibit apoptosis and maintain full proliferative activity during early brain development.
Erhardt
Nola M
NM
Department of Biology, University of Victoria, P.O. Box 1700, 3800 Finnerty Road, Victoria, BC, Canada V8W 2Y2.
Sherwood
Nancy M
NM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000196:embryology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D004247:DNA / Q000032:analysis / Q000378:metabolism; D005434:Flow Cytometry; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D009479:Neuropeptides / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors; D019311:Staurosporine / Q000633:toxicity
D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone; D004247:DNA; D019311:Staurosporine