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

Abstract

The role of FGF signaling in early epithelial dierentia-tion 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 dierentiate into cystic embryoid bodies. No epithelial dierentiation 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 PLCg-1, as compared to the wild type, while the activation of MAPK/Erk was less aected. Requirement for PI 3-kinase signaling in embryoid body dierentia-tion was demonstrated by specific inhibitors. Akt/PKB activation was abrogated by wortmannin in short-term experiments. In long-term cultures Ly294002 inhibited the dierentiation of ES cells into embryoid bodies. Our data demonstrate that for early epithelial dierentiation FGF signaling is required through the PI 3-kinase-Akt