title: Dual role of YAP and TAZ in renewal of the intestinal epithelium.
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.
authors.affiliation: 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.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Imajo
authors.affiliation: 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.
authors.forename: Miki
authors.initials: M
authors.lastname: Ebisuya
authors.affiliation: 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.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Nishida
mesh_terms: D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D001665:Binding Sites; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D020869:Gene Expression Profiling; D018014:Gene Transfer Techniques; D020397:Goblet Cells / Q000166:cytology*; D007413:Intestinal Mucosa / Q000254:growth & development*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D009124:Muscle Proteins / Q000096:biosynthesis; D010750:Phosphoproteins / Q000235:genetics*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D012038:Regeneration / Q000235:genetics / Q000502:physiology; D000090742:Serine-Threonine Kinase 3; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology*; D000091262:TEA Domain Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics; D000091102:YAP-Signaling Proteins; D000099317:Hippo Kinases
chemical_list: D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D009124:Muscle Proteins; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering; D000090742:Serine-Threonine Kinase 3; D000091262:TEA Domain Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000091102:YAP-Signaling Proteins; C000715468:Klf4 protein, mouse; C083215:Tead1 protein, mouse; C486310:Tead2 protein, mouse; C432156:Tead3 protein, mouse; C101204:Tead4 protein, mouse; C517794:Wwtr1 protein, mouse; C486223:Yap1 protein, mouse; C486363:tafazzin protein, mouse; C490501:Lats1 protein, mouse; C490660:Stk4 protein, mouse; D000099317:Hippo Kinases; C522633:LATS2 protein, mouse; C490818:Stk3 protein, mouse