Hippo signaling promotes lung epithelial lineage commitment by curbing Fgf10 and β-catenin signaling

Thomas Volckaert, Tingting Yuan, Jie Yuan, Eistine Boateng, Seantel Hopkins, Jin San Zhang, Victor J. Thannickal, Reinhard Fässler, Stijn P. De Langhe

Research output: Contribution to journalArticlepeer-review

Abstract

Organ growth and tissue homeostasis rely on the proliferation and differentiation of progenitor cell populations. In the developing lung, localized Fgf10 expression maintains distal Sox9-expressing epithelial progenitors and promotes basal cell differentiation in the cartilaginous airways. Mesenchymal Fgf10 expression is induced by Wnt signaling but inhibited by Shh signaling, and epithelial Fgf10 signaling activates β-catenin signaling. The Hippo pathway is a well-conserved signaling cascade that regulates organ size and stem/ progenitor cell behavior. Here, we show that Hippo signaling promotes lineage commitment of lung epithelial progenitors by curbing Fgf10 and β-catenin signaling. Our findings show that both inactivation of the Hippo pathway (nuclear Yap) or ablation of Yap result in increased β-catenin and Fgf10 signaling, suggesting a cytoplasmic role for Yap in epithelial lineage commitment. We further demonstrate redundant and non-redundant functions for the two nuclear effectors of the Hippo pathway, Yap and Taz, during lung development.

Original languageEnglish (US)
Article numberdev166454
JournalDevelopment (Cambridge)
Volume146
Issue number2
DOIs
StatePublished - Jan 15 2019

Keywords

  • Differentiation
  • Fgf10
  • Fgfr2
  • Hippo
  • Ilk
  • Integrin
  • Lung
  • Progenitor
  • Yap
  • β-Catenin

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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