2. Academic Validation
  3. Epithelial tension controls intestinal cell extrusion

Epithelial tension controls intestinal cell extrusion

  • Science. 2025 Sep 4;389(6764):eadr8753. doi: 10.1126/science.adr8753.
Daniel Krueger # 1 2,  Willem Kasper Spoelstra # 3,  Dirk Jan Mastebroek 1,  Rutger N U Kok 3 4,  Shanie Wu 1,  Mike Nikolaev 4,  Marie Bannier-Hélaouët 1 2,  Nikolche Gjorevski 4,  Matthias Lutolf 4,  Johan van Es 1 2,  Jeroen van Zon 3,  Sander J Tans 3 5,  Hans Clevers 1 2
Affiliations

Affiliations

  • 1 Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Centre Utrecht (UMC), Utrecht, Netherlands.
  • 2 Oncode Institute, Hubrecht Institute, Utrecht, Netherlands.
  • 3 AMOLF Institute, Amsterdam, Netherlands.
  • 4 École Polytechnique Fédérale de Lausanne/Institute of Human Biology, Basel, Switzerland.
  • 5 Bionanoscience Department, Kavli Institute of Nanoscience Delft, Delft University of Technology, Delft, Netherlands.
  • # Contributed equally.
PMID: 40906841 DOI: 10.1126/science.adr8753
Abstract

Cell extrusion is essential for homeostatic self-renewal of the intestinal epithelium. Extrusion is thought to be triggered by crowding-induced compression of cells at the intestinal villus tip. In this study, we found instead that a local "tug-of-war" competition between contractile cells regulated extrusion in the intestinal epithelium. We combined quantitative live microscopy, optogenetic induction of tissue tension, genetic perturbation of Myosin II activity, and local disruption of the basal cortex in mouse intestines and intestinal organoids. These approaches revealed that a dynamic actomyosin network generates tension throughout the intestinal villi, including the villus tip region. Mechanically weak cells unable to maintain this tension underwent extrusion. Thus, epithelial barrier integrity depends on intercellular mechanics.

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