YAP/TAZ and Hedgehog Coordinate Growth and Patterning in Gastrointestinal Mesenchyme

Dev Cell. 2017 Oct 9;43(1):35-47.e4. doi: 10.1016/j.devcel.2017.08.019. Epub 2017 Sep 21.


YAP/TAZ are the major mediators of mammalian Hippo signaling; however, their precise function in the gastrointestinal tract remains poorly understood. Here we dissect the distinct roles of YAP/TAZ in endodermal epithelium and mesenchyme and find that, although dispensable for gastrointestinal epithelial development and homeostasis, YAP/TAZ function as the critical molecular switch to coordinate growth and patterning in gut mesenchyme. Our genetic analyses reveal that Lats1/2 kinases suppress expansion of the primitive mesenchymal progenitors, where YAP activation also prevents induction of the smooth muscle lineage through transcriptional repression of Myocardin. During later development, zone-restricted downregulation of YAP/TAZ provides the positional cue and allows smooth muscle cell differentiation induced by Hedgehog signaling. Taken together, our studies identify the mesenchymal requirement of YAP/TAZ in the gastrointestinal tract and highlight the functional interplays between Hippo and Hedgehog signaling underlying temporal and spatial control of tissue growth and specification in developing gut.

Keywords: Hedgehog; Hippo; Lats1/2; YAP/TAZ; differentiation; growth; intestine; mesenchyme; patterning; smooth muscle.

MeSH terms

  • Acyltransferases
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Cycle Proteins
  • Cell Differentiation / physiology*
  • Epithelium / metabolism*
  • Epithelium / pathology
  • Gastrointestinal Tract / metabolism*
  • Hedgehog Proteins / metabolism*
  • Mesoderm / metabolism*
  • Mice, Transgenic
  • Nuclear Proteins / metabolism
  • Phosphoproteins / metabolism*
  • Signal Transduction / physiology
  • Trans-Activators / metabolism
  • Transcription Factors / metabolism*
  • YAP-Signaling Proteins


  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Hedgehog Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • Trans-Activators
  • Transcription Factors
  • YAP-Signaling Proteins
  • Yap1 protein, mouse
  • myocardin
  • Acyltransferases
  • tafazzin protein, mouse