Competitive elimination of ZO-1/ZO-2-deficient cells regulates epithelial barrier homeostasis

SummaryEpithelia cover the body and form a barrier to segregate the internal body from the external environment. Epithelial tissues contact the external environment and are exposed to various stresses that are potentially deleterious for the epithelial barrier1. However, how focal epithelial barrier defects are detected and repaired to maintain epithelial barrier homeostasis remains poorly understood. We co-culturedZO-1/ZO-2double-knockout (DKO) MDCK II cells, which lack tight junctions, with wild-type MDCK II cells, to understand how epithelial cells respond to focal epithelial barrier defects. When co-cultured with wild-type cells,ZO-1/ZO-2DKO cells were selectively eliminated by induction of apoptosis. The elimination depended on a purse-string-like contraction of supracellular actomyosin cables formed at the clone boundary, regulated by ROCK. Furthermore, Hippo signaling and adherens junctions in the surrounding wild-type cells were required to eliminateZO-1/ZO-2DKO cells. These results demonstrate that selective elimination of ZO-1/ZO-2-deficient cells by cell competition regulates epithelial barrier homeostasis.In briefOtani et al. reveal that epithelial barrier homeostasis is regulated by cell competition-mediated elimination of ZO-1/ZO-2-deficient cells. Supracellular actomyosin cables form at the clone boundary and constrict in a purse-string-like manner to eliminate the ‘loser’ cells. Mechanosensing in the winning cells is required to eliminate the ‘loser’ cells.HighlightsZO-1/ZO-2-deficient cells are eliminated by cell competitionActomyosin cables form in the winning cells at the clone boundaryA purse-string-like contraction of actomyosin cables compresses the losing cellsMechanosensing in the winning cells is important to eliminate the ‘loser’ cells