Epithelial tension controls intestinal cell extrusion
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.
Authors
- Matthias P. Lütolf (ORCID: https://orcid.org/0000-0002-5898-305X)
- Johan H. van Es (ORCID: https://orcid.org/0000-0002-1338-7078)
- Jeroen S. van Zon (ORCID: https://orcid.org/0000-0002-6021-2924)
- Daniel Krueger (ORCID: https://orcid.org/0000-0003-1139-7755)
- Nikolche Gjorevski (ORCID: https://orcid.org/0000-0001-8320-0443)
- Sander J. Tans (ORCID: https://orcid.org/0000-0002-7131-2568)
- Hans Clevers (ORCID: https://orcid.org/0000-0002-3077-5582)
- Mikhail Nikolaev (ORCID: https://orcid.org/0000-0001-5955-900X)
- Dirk Jan Mastebroek (ORCID: https://orcid.org/0000-0002-1015-1481)
- Rutger N.U. Kok (ORCID: https://orcid.org/0000-0002-6214-681X)
- Marie Bannier-Hélaouët (ORCID: https://orcid.org/0000-0002-0549-3903)
- Willem Kasper Spoelstra (ORCID: https://orcid.org/0000-0002-7940-0829)
- Sanlan Wu
Institutions
- Royal Netherlands Academy of Arts and Sciences (NL)
- Institute for Atomic and Molecular Physics (NL)
- Oncode Institute (NL)
- École Polytechnique Fédérale de Lausanne (CH)
- Delft University of Technology (NL)
Publication Details
- Journal
- Science
- Published
- 2025-09-04
- DOI
- https://doi.org/10.1126/science.adr8753
- Citations
- 6
- Primary Topic
- Cellular Mechanics and Interactions
- Type
- article
- Field-Weighted Citation Impact
- 6.91