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

Publication date: Available online 21 September 2017
Source:Developmental Cell
Author(s): Jennifer L. Cotton, Qi Li, Lifang Ma, Joo-Seop Park, Jiayi Wang, Jianhong Ou, Lihua J. Zhu, Y. Tony Ip, Randy L. Johnson, Junhao Mao
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.

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The precise function of the Hippo effectors, YAP/TAZ, in the gastrointestinal tract remains elusive. Cotton et al. identify a key role of YAP/TAZ in coordination of growth and patterning in gut mesenchyme and highlight the functional interplay between Hippo and Hedgehog signaling underlying the spatial-temporal control of smooth muscle specification.


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