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

Developmental cell | Oct 9, 2017

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.

Pubmed ID: 28943241 RIS Download

Mesh terms: Adaptor Proteins, Signal Transducing | Animals | Cell Differentiation | Epithelium | Gastrointestinal Tract | Hedgehog Proteins | Mesoderm | Mice, Transgenic | Nuclear Proteins | Phosphoproteins | Signal Transduction | Trans-Activators | Transcription Factors

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Associated grants

  • Agency: NIDDK NIH HHS, Id: R01 DK083450
  • Agency: NIDDK NIH HHS, Id: R01 DK099510
  • Agency: NIDDK NIH HHS, Id: R01 DK100315
  • Agency: NIGMS NIH HHS, Id: R01 GM107457

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