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

Vivian W Y Wong | Daniel E Stange | Mahalia E Page | Simon Buczacki | Agnieszka Wabik | Satoshi Itami | Marc van de Wetering | Richard Poulsom | Nicholas A Wright | Matthew W B Trotter | Fiona M Watt | Doug J Winton | Hans Clevers | Kim B Jensen
Nature cell biology | 2012

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.

Pubmed ID: 22388892

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Associated grants

  • Agency: Wellcome Trust, United Kingdom
    Id: 079249
  • Agency: Wellcome Trust, United Kingdom
    Id: 088454
  • Agency: Medical Research Council, United Kingdom
    Id: G0800784

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