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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.

Original publication

DOI

10.1038/ncb2464

Type

Journal article

Journal

Nat Cell Biol

Publication Date

04/03/2012

Volume

14

Pages

401 - 408

Keywords

Animals, Feedback, Physiological, Gene Expression Profiling, Genes, erbB, Homeostasis, Intestines, Membrane Glycoproteins, Mice, Mice, Inbred Strains, Mice, Knockout, Nerve Tissue Proteins, Receptor, ErbB-2, Signal Transduction, Stem Cell Niche, Stem Cells