Lrig1 controls intestinal stem-cell homeostasis by negative regulation of ErbB signalling
| Autor: | Marc van de Wetering, Vivian W. Y. Wong, Richard Poulsom, Agnieszka Wabik, Kim B. Jensen, Hans Clevers, Fiona M. Watt, Matthew Trotter, Daniel E. Stange, Simon J.A. Buczacki, Mahalia E. Page, Doug J. Winton, Satoshi Itami, Nicholas A. Wright |
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| Přispěvatelé: | Hubrecht Institute for Developmental Biology and Stem Cell Research |
| Rok vydání: | 2011 |
| Předmět: |
Intestinal stem cell homeostasis
Receptor ErbB-2 Regulator Mice Inbred Strains Nerve Tissue Proteins Biology Article 03 medical and health sciences Mice 0302 clinical medicine ErbB Animals Homeostasis Stem Cell Niche Receptor 030304 developmental biology Feedback Physiological Mice Knockout 0303 health sciences Membrane Glycoproteins Gene Expression Profiling Stem Cells Genes erbB Wnt signaling pathway Cell Biology Intestinal epithelium Cell biology Intestines 030220 oncology & carcinogenesis Signal transduction Stem cell Signal Transduction |
| Zdroj: | Nature cell biology Nature Cell Biology, 14(4), 401-408. Nature Publishing Group |
| ISSN: | 1476-4679 1465-7392 |
| Popis: | Maintenance of adult tissues is carried out by stem cells and is sustained throughout life in a highly ordered manner. Homeostasis within the stem-cell compartment is governed by positive- and negative-feedback regulation of instructive extrinsic and intrinsic signals. ErbB signalling is a prerequisite for maintenance of the intestinal epithelium following injury and tumour formation. As ErbB-family ligands and receptors are highly expressed within the stem-cell niche, we hypothesize that strong endogenous regulators must control the pathway in the stem-cell compartment. Here we show that Lrig1, a negative-feedback regulator of the ErbB receptor family, is highly expressed by intestinal stem cells and controls the size of the intestinal stem-cell niche by regulating the amplitude of growth-factor signalling. Intestinal stem-cell maintenance has so far been attributed to a combination of Wnt and Notch activation and Bmpr inhibition. Our findings reveal ErbB activation as a strong inductive signal for stem-cell proliferation. This has implications for our understanding of ErbB signalling in tissue development and maintenance and the progression of malignant disease. |
| Databáze: | OpenAIRE |
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