Lrig1 controls intestinal stem-cell homeostasis by negative regulation of ErbB signalling
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
Maintenance of adult tissues is carried out by stem cells and is sustained throughout life in a highly ordered manner(1,2). Homeostasis within the stem-cell compartment is governed by positive- and negative-feedback regulation of instructive extrinsic and intrinsic signals(3,4). ErbB signalling is a prerequisite for maintenance of the intestinal epithelium following injury and tumour formation(5,6). As ErbB-family ligands and receptors are highly expressed within the stem-cell niche(7), 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(8-10), 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(11-13). 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.
Details
Original language | English |
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Pages (from-to) | 401-+ |
Number of pages | 16 |
Journal | Nature cell biology |
Volume | 14 |
Issue number | 4 |
Publication status | Published - Apr 2012 |
Peer-reviewed | Yes |
External IDs
PubMed | 22388892 |
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Scopus | 84859430024 |
Keywords
Keywords
- Receptor tyrosine kinase, Lgr5, Population, Pattern, Maintenance, Inhibition, Adenomas, Niches, Crypts, Level