Epithelial tension controls intestinal cell extrusion.

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.