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FGF9 and FGF10 activate distinct signaling pathways to direct lung epithelial specification and branching

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Science Signaling  03 Mar 2020:
Vol. 13, Issue 621, eaay4353
DOI: 10.1126/scisignal.aay4353

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Differential FGF signaling in the same tissue

Fibroblast growth factors (FGFs) stimulate various intracellular signaling pathways through a limited number of receptors (FGFRs). Yin and Ornitz found that activation of distinct FGFRs by FGF9 and FGF10 preferentially activated distinct intracellular signaling pathways in the embryonic mouse lung epithelium, resulting in different developmental effects. Whereas FGF9 promoted distal epithelial fate specification and inhibited epithelial differentiation, FGF10 promoted epithelial proliferation and differentiation. Mechanistically, FGF9 activated phosphoinositide 3-kinase (PI3K) signaling through FGFR3, whereas FGF10 activated mitogen-activated protein kinase (MAPK) signaling through FGFR2b. Thus, two different FGFRs can function in the same cell type and transmit distinct signals with distinct phenotypic outcomes.

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