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

Research output: Contribution to journalJournal articleResearch

  • 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
  • Jensen, Kim Bak
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 languageEnglish
JournalNature Cell Biology
Volume14
Issue number4
Pages (from-to)401-8
Number of pages8
ISSN1465-7392
DOIs
Publication statusPublished - Apr 2012
Externally publishedYes

    Research areas

  • 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

ID: 94414105