PACAP decides neuronal laminar fate via PKA signaling in the developing cerebral cortex.
Laminar formation in the developing cerebral cortex requires the precisely regulated generation of phenotype-specified neurons. To test the possible involvement of pituitary adenylate cyclase-activating polypeptide (PACAP) in this formation, we investigated the effects of PACAP administered into the telencephalic ventricular space of 13.5-day-old mouse embryos. PACAP partially inhibited the proliferation of cortical progenitors and altered the position and gene-expression profiles of newly generated neurons otherwise expected for layer IV to those of neurons for the deeper layers, V and VI, of the cerebral cortex. The former and latter effects were seen only when the parent progenitor cells were exposed to PACAP in the later and in earlier G1 phase, respectively; and these effects were suppressed by co-treatment with a protein kinase A (PKA) inhibitor. These observations suggest that PACAP participates in the processes forming the neuronal laminas in the developing cortex via the intracellular PKA pathway.
Ohtsuka
Masanari
M
Laboratory of Molecular Biology, Department of Biofunctional Analysis, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan.
Fukumitsu
Hidefumi
H
Furukawa
Shoei
S
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002453:Cell Cycle; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000201:enzymology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000201:enzymology / Q000502:physiology*; D010766:Phosphorylation; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D047428:Protein Kinase Inhibitors; D017868:Cyclic AMP-Dependent Protein Kinases