Fibroblast growth factor-2 converts PACAP growth action on embryonic hindbrain precursors from stimulation to inhibition

J Neurosci Res. 2002 Mar 1;67(5):566-73. doi: 10.1002/jnr.10153.

Abstract

Pituitary adenylyl cyclase activating peptide (PACAP) has been shown either to stimulate or to inhibit neural cell proliferation depending on the origin of the cell population. We show here that, depending on the presence or absence of fibroblast growth factor-2 (FGF-2, also called basic FGF), PACAP may either stimulate or inhibit DNA synthesis in neural precursors isolated from embryonic day 10.5 mouse hindbrain. In the absence of FGF-2, PACAP stimulated 3H-thymidine incorporation in a dose-dependent manner. This stimulatory action was unaffected by antagonists of protein kinases A and C but was abolished in the presence of the MEK1/2 antagonist PD98059. In contrast, when FGF-2 was present, PACAP inhibited DNA synthesis. This inhibitory action was insensitive to PD98059 but was fully blocked by the protein kinase A (PKA) inhibitor H89. The differential blockades by MEK1/2 and PKA inhibitors indicate that the FGF-2-induced switch in PACAP action on DNA synthesis was accomplished by a change in PACAP signaling pathways. We hypothesize that the actions of PACAP in the specific parts of the developing nervous system are determined in part by the presence or absence of FGFs and other growth factors.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing / genetics
  • Animals
  • Cell Division / drug effects
  • Cell Division / physiology*
  • Cells, Cultured
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • DNA / biosynthesis
  • DNA / drug effects
  • Female
  • Fetus
  • Fibroblast Growth Factor 2 / deficiency*
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / pharmacology
  • Gene Expression Regulation, Developmental / physiology
  • MAP Kinase Kinase 1
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Neurons / drug effects
  • Neurons / enzymology*
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • Neuropeptides / pharmacology
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Pregnancy
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Pituitary Hormone / drug effects
  • Receptors, Pituitary Hormone / genetics
  • Receptors, Pituitary Hormone / metabolism
  • Rhombencephalon / drug effects
  • Rhombencephalon / embryology*
  • Rhombencephalon / enzymology*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Stem Cells / drug effects
  • Stem Cells / enzymology*

Substances

  • Adcyap1 protein, mouse
  • Neuropeptides
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • RNA, Messenger
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Pituitary Hormone
  • Fibroblast Growth Factor 2
  • DNA
  • Protein Serine-Threonine Kinases
  • Cyclic AMP-Dependent Protein Kinases
  • MAP Kinase Kinase 1
  • Map2k1 protein, mouse
  • Mitogen-Activated Protein Kinase Kinases