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. © 2012 Macmillan Publishers Limited. All rights reserved.
CITATION STYLE
Wong, V. W. Y., Stange, D. E., Page, M. E., Buczacki, S., Wabik, A., Itami, S., … Jensen, K. B. (2012). Lrig1 controls intestinal stem-cell homeostasis by negative regulation of ErbB signalling. Nature Cell Biology, 14(4), 401–408. https://doi.org/10.1038/ncb2464
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