Lrig1 controls intestinal stem-cell homeostasis by negative regulation of ErbB signalling

Abstract

Lrig1, a transmembrane glycoprotein, has previously been shown to inhibit ErbB signalling. Jensen and colleagues show that Lrig1 controls the size of the intestinal stem-cell niche by modulating the amplitude of ErbB signalling. Thus, ErbB activation acts in concert with Wnt, Notch and Bmpr inhibition, to modulate stem-cell proliferation in the crypt. Maintenance of adult tissues is carried out by stem cells and is sustained throughout life in a highly ordered manner1,2. Homeostasis within the stem-cell compartment is governed by positive- and negative-feedback regulation of instructive extrinsic and intrinsic signals3,4. ErbB signalling is a prerequisite for maintenance of the intestinal epithelium following injury and tumour formation5,6. As ErbB-family ligands and receptors are highly expressed within the stem-cell niche7, 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 family8,9,10, 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 inhibition11,12,13. 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.

Cite this article

Wong, V., Stange, D., Page, M. et al. Lrig1 controls intestinal stem-cell homeostasis by negative regulation of ErbB signalling. Nat Cell Biol 14, 401–408 (2012). https://doi.org/10.1038/ncb2464

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