ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Pro- and anti-mitogenic actions of pituitary adenylate cyclase-activating polypeptide in developing cerebral cortex: potential mediation by developmental switch of PAC1 receptor mRNA isoforms.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- Article
- Long-term Effects of the pituitary-adenylate cyclase-activating Polypeptide (PACAP38) in the Adult Mouse Retina: Microglial Activation and Induction of Neural Proliferation.Neurochemical research · 2023Article
- Targeting VIP and PACAP Receptor Signaling: New Insights into Designing Drugs for the PACAP Subfamily of Receptors.International journal of molecular sciences · 2022Review
- PACAP-PAC1 Signaling Regulates Serotonin 2A Receptor Internalization.Frontiers in endocrinology · 2021Article
- Splice-specific deficiency of the PTSD-associated gene PAC1 leads to a paradoxical age-dependent stress behavior.Scientific reports · 2020Article
- Pleiotropic pituitary adenylate cyclase-activating polypeptide (PACAP): Novel insights into the role of PACAP in eating and drug intake.Brain research · 2020Review
- Role of pituitary adenylate cyclase-activating polypeptide in modulating hypothalamic-pituitary system.Reproductive medicine and biology · 2018Review
- Review on PACAP-Induced Transcriptomic and Proteomic Changes in Neuronal Development and Repair.International journal of molecular sciences · 2018Review
- Rapid Detection of Neurodevelopmental Phenotypes in Human Neural Precursor Cells (NPCs).Journal of visualized experiments : JoVE · 2018Article
- Early Neurobehavioral Development of Mice Lacking Endogenous PACAP.Journal of molecular neuroscience : MN · 2017Article
- PACAP Is Protective in a Rat Model of Retinopathy of Prematurity.Journal of molecular neuroscience : MN · 2016Article
- Convergent phosphomodulation of the major neuronal dendritic potassium channel Kv4.2 by pituitary adenylate cyclase-activating polypeptide.Neuropharmacology · 2016Article
- Kalirin-9 and Kalirin-12 Play Essential Roles in Dendritic Outgrowth and Branching.Cerebral cortex (New York, N.Y. : 1991) · 2015Article
- Zac1 Regulates the Differentiation and Migration of Neocortical Neurons via Pac1.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- PACAP modulation of calcium ion activity in developing granule cells of the neonatal mouse olfactory bulb.Journal of neurophysiology · 2015Article
- Structural and morphometric comparison of the molar teeth in pre-eruptive developmental stage of PACAP-deficient and wild-type mice.Journal of molecular neuroscience : MN · 2014Article
- Pituitary adenylate cyclase-activating polypeptide (PACAP) signalling enhances osteogenesis in UMR-106 cell line.Journal of molecular neuroscience : MN · 2014Article
- Investigation of PACAP Fragments and Related Peptides in Chronic Retinal Hypoperfusion.Journal of ophthalmology · 2014Article
- Development-related alternative splicing of PAC1 receptor: a key player in schizophrenia?Frontiers in molecular neuroscience · 2013Article
- Activation of PAC1 Receptors in Rat Cerebellar Granule Cells Stimulates Both Calcium Mobilization from Intracellular Stores and Calcium Influx through N-Type Calcium Channels.Frontiers in endocrinology · 2013Article
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
During corticogenesis, pituitary adenylate cyclase-activating polypeptide (PACAP; ADCYAP1) may contribute to proliferation control by activating PAC1 receptors of neural precursors in the embryonic ventricular zone. PAC1 receptors, specifically the hop and short isoforms, couple differentially to and activate distinct pathways that produce pro- or anti-mitogenic actions. Previously, we found that PACAP was an anti-mitogenic signal from embryonic day 13.5 (E13.5) onward both in culture and in vivo and activated cAMP signaling through the short isoform. However, we now find that mice deficient in PACAP exhibited a decrease in the BrdU labeling index (LI) in E9.5 cortex, suggesting that PACAP normally promotes proliferation at this stage. To further define mechanisms, we established a novel culture model in which the viability of very early cortical precursors (E9.5 mouse and E10.5 rat) could be maintained. At this stage, we found that PACAP evoked intracellular calcium fluxes and increased phospho-PKC levels, as well as stimulated G1 cyclin mRNAs and proteins, S-phase entry, and proliferation without affecting cell survival. Significantly, expression of hop receptor isoform was 24-fold greater than the short isoform at E10.5, a ratio that was reversed at E14.5 when short expression was 15-fold greater and PACAP inhibited mitogenesis. Enhanced hop isoform expression, elicited by in vitro treatment of E10.5 precursors with retinoic acid, correlated with sustained pro-mitogenic action of PACAP beyond the developmental switch. Conversely, depletion of hop receptor using short-hairpin RNA abolished PACAP mitogenic stimulation at E10.5. These observations suggest that PACAP elicits temporally specific effects on cortical proliferation via developmentally regulated expression of specific receptor isoforms.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.