PACAP/PAC1 autocrine system promotes proliferation and astrogenesis in neural progenitor cells

Glia. 2007 Feb;55(3):317-27. doi: 10.1002/glia.20461.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism*
  • Autocrine Communication / physiology
  • Bromodeoxyuridine
  • Calcium Signaling / physiology
  • Cell Differentiation / physiology*
  • Cell Lineage / physiology
  • Cell Proliferation*
  • Cell Shape / drug effects
  • Cell Shape / physiology
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / embryology
  • Cerebral Cortex / metabolism
  • GTP-Binding Protein alpha Subunits, Gq-G11 / drug effects
  • GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Neurons / cytology
  • Neurons / metabolism
  • Pituitary Adenylate Cyclase-Activating Polypeptide / metabolism*
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Type C Phospholipases / drug effects
  • Type C Phospholipases / metabolism

Substances

  • Adcyap1r1 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
  • Type C Phospholipases
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Bromodeoxyuridine