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

Publisher: Macmillan Magazines Ltd Country of Publication: England NLM ID: 100890575 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4679 (Electronic) Linking ISSN: 14657392 NLM ISO Abbreviation: Nat Cell Biol Subsets: MEDLINE

Original Publication: London : Macmillan Magazines Ltd., [1999-

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

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: Nat Cell Biol. 2015 Jan;17(1):5-6. (PMID: 25679030)

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GEO GSE45155

0 (Adaptor Proteins, Signal Transducing)
0 (Cell Cycle Proteins)
0 (DNA-Binding Proteins)
0 (Klf4 protein, mouse)
0 (Kruppel-Like Factor 4)
0 (Kruppel-Like Transcription Factors)
0 (Muscle Proteins)
0 (Phosphoproteins)
0 (RNA, Small Interfering)
0 (TEA Domain Transcription Factors)
0 (Tead1 protein, mouse)
0 (Tead2 protein, mouse)
0 (Tead3 protein, mouse)
0 (Tead4 protein, mouse)
0 (Trans-Activators)
0 (Transcription Factors)
0 (Tumor Suppressor Proteins)
0 (Wwtr1 protein, mouse)
0 (YAP-Signaling Proteins)
0 (Yap1 protein, mouse)
EC 2.3.- (Acyltransferases)
EC 2.3.- (tafazzin protein, mouse)
EC 2.7.1.- (Lats1 protein, mouse)
EC 2.7.1.- (Stk4 protein, mouse)
EC 2.7.11.1 (LATS2 protein, mouse)
EC 2.7.11.1 (Protein Serine-Threonine Kinases)
EC 2.7.11.1 (Serine-Threonine Kinase 3)
EC 2.7.11.1 (Stk3 protein, mouse)

Date Created: 20141223 Date Completed: 20160419 Latest Revision: 20220408

20240829

10.1038/ncb3084

25531778