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Nat Cell Biol. 2015 Jan;17(1):7-19. doi: 10.1038/ncb3084. Epub 2014 Dec 22.

Dual role of YAP and TAZ in renewal of the intestinal epithelium.

Author information

1
1] Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan [2] JST, CREST, Chiyoda-ku, Tokyo 102-0075, Japan [3] Laboratory of Bioimaging and Cell Signaling, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
2
1] Career-Path Promotion Unit for Young Life Scientist, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan [2] Laboratory for Reconstitutive Developmental Biology, RIKEN Center for Developmental Biology, Kobe, Hyogo 650-0047, Japan.
3
1] Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan [2] JST, CREST, Chiyoda-ku, Tokyo 102-0075, Japan.

Abstract

The rapidly self-renewing intestinal epithelium represents an exquisite model for stem cell biology. So far, genetic studies in mice have uncovered crucial roles for several signalling pathways in the tissue. Here we show, by using intestine-specific gene transfer (iGT), that Hippo signalling effectors, YAP and TAZ, promote both the proliferation of intestinal stem/progenitor cells and their differentiation into goblet cells. These functions of YAP/TAZ are regulated by the upstream Hippo pathway kinases MST1/2 and LATS1/2. Moreover, we identify TEADs and Klf4 as partner transcription factors of YAP/TAZ in the proliferation and differentiation processes, respectively. These results indicate that Hippo signalling plays a dual role in renewal of the intestinal epithelium through the regulation of two different processes, stem/progenitor cell proliferation and differentiation into goblet cells, using two different types of transcription factor. Moreover, iGT should provide a robust platform to elucidate molecular mechanisms of intestinal epithelium self-renewal.

Comment in

PMID:
25531778
DOI:
10.1038/ncb3084
[Indexed for MEDLINE]

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