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

Masamichi Imajo; Miki Ebisuya; Eisuke Nishida

doi:10.1038/ncb3084

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

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

Authors

Masamichi Imajo¹, Miki Ebisuya², Eisuke Nishida³

Affiliations

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.

PMID: 25531778
DOI: 10.1038/ncb3084

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acyltransferases
Adaptor Proteins, Signal Transducing / genetics*
Animals
Binding Sites
Cell Cycle Proteins
Cell Differentiation
Cell Proliferation
Cells, Cultured
DNA-Binding Proteins / biosynthesis
Gene Expression Profiling
Gene Transfer Techniques
Goblet Cells / cytology*
Intestinal Mucosa / growth & development*
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors / biosynthesis
Kruppel-Like Transcription Factors / genetics
Male
Mice
Mice, Inbred C57BL
Mice, Inbred ICR
Muscle Proteins / biosynthesis
Phosphoproteins / genetics*
Protein Binding
Protein Serine-Threonine Kinases / genetics
RNA Interference
RNA, Small Interfering
Regeneration / genetics
Regeneration / physiology
Serine-Threonine Kinase 3
Signal Transduction / physiology
Stem Cells / cytology*
TEA Domain Transcription Factors
Trans-Activators
Transcription Factors / biosynthesis
Transcription Factors / genetics*
Tumor Suppressor Proteins / genetics
YAP-Signaling Proteins

Substances

Adaptor Proteins, Signal Transducing
Cell Cycle Proteins
DNA-Binding Proteins
Klf4 protein, mouse
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors
Muscle Proteins
Phosphoproteins
RNA, Small Interfering
TEA Domain Transcription Factors
Tead1 protein, mouse
Tead2 protein, mouse
Tead3 protein, mouse
Tead4 protein, mouse
Trans-Activators
Transcription Factors
Tumor Suppressor Proteins
Wwtr1 protein, mouse
YAP-Signaling Proteins
Yap1 protein, mouse
Acyltransferases
tafazzin protein, mouse
Lats1 protein, mouse
Stk4 protein, mouse
LATS2 protein, mouse
Protein Serine-Threonine Kinases
Serine-Threonine Kinase 3
Stk3 protein, mouse

Associated data

GEO/GSE45155