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

VWY Wong, DE Stange, ME Page, S Buczacki… - Nature cell …, 2012 - nature.com
VWY Wong, DE Stange, ME Page, S Buczacki, A Wabik, S Itami, M Van De Wetering…
Nature cell biology, 2012nature.com
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 …
Abstract
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.
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