Abstract
The Pituitary adenylate cyclase-activating peptide (PACAP) ligand/type 1 receptor (PAC1) system regulates neurogenesis and gliogenesis. It has been well established that the PACAP/PAC1 system induces differentiation of neural progenitor cells (NPCs) through the Gs-mediated cAMP-dependent signaling pathway. However, it is unknown whether this ligand/receptor system has a function in proliferation of NPCs. In this study, we identified that PACAP and PAC1 were highly expressed and co-localized in NPCs of mouse cortex at embryonic day 14.5 (E14.5) and found that the PACAP/PAC1 system potentiated growth factor-induced proliferation of mouse cortical NPCs at E14.5 via Gq-, but not Gs-, mediated PLC/IP3-dependent signaling pathway in an autocrine manner. Moreover, PAC1 activation induced elongation of cellular processes and a stellate morphology in astrocytes that had the bromodeoxyuridine (BrdU)-incorporating ability of NPCs. Consistent with this notion, we determined that the most BrdU positive NPCs differentiated to astrocytes through PAC1 signaling. These results suggest that the PACAP/PAC1 system may play a dual role in neural/glial progenitor cells not only differentiation but also proliferation in the cortical astrocyte lineage via Ca2+-dependent signaling pathways through PAC1.
Copyright 2006 Wiley-Liss, Inc.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Astrocytes / cytology
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Astrocytes / metabolism*
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Autocrine Communication / physiology
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Bromodeoxyuridine
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Calcium Signaling / physiology
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Cell Differentiation / physiology*
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Cell Lineage / physiology
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Cell Proliferation*
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Cell Shape / drug effects
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Cell Shape / physiology
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Cells, Cultured
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Cerebral Cortex / cytology
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Cerebral Cortex / embryology
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Cerebral Cortex / metabolism
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GTP-Binding Protein alpha Subunits, Gq-G11 / drug effects
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GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism
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Intercellular Signaling Peptides and Proteins / metabolism
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Intercellular Signaling Peptides and Proteins / pharmacology
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Mice
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Mice, Inbred C57BL
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Neurons / cytology
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Neurons / metabolism
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Pituitary Adenylate Cyclase-Activating Polypeptide / metabolism*
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Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / metabolism*
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Stem Cells / cytology
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Stem Cells / metabolism*
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Type C Phospholipases / drug effects
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Type C Phospholipases / metabolism
Substances
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Adcyap1r1 protein, mouse
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Intercellular Signaling Peptides and Proteins
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Pituitary Adenylate Cyclase-Activating Polypeptide
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Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
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Type C Phospholipases
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GTP-Binding Protein alpha Subunits, Gq-G11
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Bromodeoxyuridine