Robustness of epithelial sealing is an emerging property of local ERK feedback driven by cell elimination
Résumé
10 While the pathways regulating apoptosis and cell extrusion are rather well 11 described 1,2 , what regulates the precise spatio-temporal distribution of cell 12 elimination in tissues remains largely unknown. This is particularly relevant for 13 epithelia with high rates of cell elimination, a widespread situation during 14 embryogenesis 3-6 and epithelial homeostasis 7 , where concomitant death of 15 neighbours could impair the maintenance of epithelial sealing. However, the extent 16 to which epithelial tissues can cope with concomitant cell death, and whether any 17 mechanism regulates such occurrence have never been explored so far. Here, 18 using the Drosophila pupal notum (a single layer epithelium) and a new 19 optogenetic tool to trigger caspase activation and cell extrusion, we first show that 20 concomitant death of clusters of at least three cells is sufficient to transiently 21 impair epithelial sealing. Such clustered extrusion was almost never observed in 22 vivo, suggesting the existence of a mechanism preventing concomitant elimination 23 of neighbours. Statistical analysis and simulations of cell death distribution in the 24 notum highlighted a transient and local protective phase occurring near every 25 dying cell. This protection is driven by a transient activation of ERK in the direct 26 neighbours of extruding cells which reverts caspase activation and prevents 27 elimination of cells in clusters. Altogether, this study demonstrates that the 28 distribution of cell elimination in epithelia is an emerging property of transient and 29
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