Fibroblast growth factor (FGF) signaling through PI 3-kinase and Akt/PKB is required for embryoid body differentiation

Oncogene. 2000 Aug 3;19(33):3750-6. doi: 10.1038/sj.onc.1203726.

Abstract

The role of FGF signaling in early epithelial differentiation was investigated in ES (embryonic stem) cell derived embryoid bodies. A dominant negative fibroblast growth factor receptor (FGFR) mutation was created by stably introducing into ES cells an Fgfr2 cDNA, truncated in its enzymatic domains. These cells failed to differentiate into cystic embryoid bodies. No epithelial differentiation and cavitation morphogenesis could be observed, in the mutant, although its rate of cell proliferation remained unchanged. This phenotype was associated with a significant decrease in the activation of Akt/PKB and PLCgamma-1, as compared to the wild type, while the activation of MAPK/Erk was less affected. Requirement for PI 3-kinase signaling in embryoid body differentiation was demonstrated by specific inhibitors. Akt/PKB activation was abrogated by wortmannin in short-term experiments. In long-term cultures Ly294002 inhibited the differentiation of ES cells into embryoid bodies. Our data demonstrate that for early epithelial differentiation FGF signaling is required through the PI 3-kinase-Akt/ PKB pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Enzyme Activation
  • Epithelium
  • Fibroblast Growth Factors / metabolism*
  • Gene Expression
  • Isoenzymes / metabolism
  • Mutagenesis
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Phospholipase C gamma
  • Protein-Serine-Threonine Kinases*
  • Protein-Tyrosine Kinases*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • Receptor Protein-Tyrosine Kinases / biosynthesis
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, Fibroblast Growth Factor, Type 2
  • Receptor, Fibroblast Growth Factor, Type 3
  • Receptor, Fibroblast Growth Factor, Type 4
  • Receptors, Fibroblast Growth Factor / biosynthesis
  • Receptors, Fibroblast Growth Factor / genetics
  • Signal Transduction*
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Type C Phospholipases / metabolism

Substances

  • Isoenzymes
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factors
  • Protein-Tyrosine Kinases
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, Fibroblast Growth Factor, Type 2
  • Receptor, Fibroblast Growth Factor, Type 3
  • Receptor, Fibroblast Growth Factor, Type 4
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Type C Phospholipases
  • Phospholipase C gamma