Dual role of YAP and TAZ in renewal of the intestinal epithelium
Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung
Beitragende
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.
Details
Originalsprache | Englisch |
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Seiten (von - bis) | 7-19 |
Seitenumfang | 13 |
Fachzeitschrift | Nature cell biology |
Jahrgang | 17 |
Ausgabenummer | 1 |
Publikationsstatus | Veröffentlicht - Jan. 2015 |
Peer-Review-Status | Ja |
Extern publiziert | Ja |
Externe IDs
Scopus | 85018698979 |
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Schlagworte
Schlagwörter
- 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, 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, Serine-Threonine Kinase 3, Signal Transduction/physiology, Stem Cells/cytology, TEA Domain Transcription Factors, Trans-Activators, Transcription Factors/biosynthesis, Tumor Suppressor Proteins/genetics, YAP-Signaling Proteins