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 PLCĪ³-1, 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.
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Acknowledgements
Our thanks are due to Esther Arman for the in situ hybridization technique. This study was in part supported by the Israel Science Fund. P Lonai is the John Roberts Professor of Cancer Research at the Weizmann Institute.
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Chen, Y., Li, X., Eswarakumar, V. et al. Fibroblast growth factor (FGF) signaling through PI 3-kinase and Akt/PKB is required for embryoid body differentiation. Oncogene 19, 3750ā3756 (2000). https://doi.org/10.1038/sj.onc.1203726
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DOI: https://doi.org/10.1038/sj.onc.1203726
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