Robustness of epithelial sealing is an emerging property of local ERK feedback driven by cell elimination

What regulates the spatiotemporal distribution of cell elimination in tissues remains largely unknown. This is particularly relevant for epithelia with highratesofcelleliminationwhere simultaneousdeathof neighboringcells could impair epithelial sealing. Here, using the Drosophila pupal notum(a single-layer epithelium) and a newoptogenetic tool to trigger caspase activation and cell extrusion, we first showed that death of clusters of at least three cells impaired epithelial sealing; yet, such clusters were almost never observed in vivo. Accordingly, statistical analysis and simulations of cell death distribution highlighted a transient and local protective phase occurring near every cell death. This protection is driven by a transient activation of ERK in cells neighboring extruding cells, which inhibits caspase activation and prevents elimination of cells in clusters. This suggests that the robustness of epithelia with high rates of cell elimination is an emerging property of local ERK feedback.

Automated summary

Research using Drosophila pupal notum as a model shows that clusters of cell death impair epithelial sealing, but such clusters are rarely observed in vivo. Statistical analysis and simulations reveal a transient and local protective phase near each cell death, driven by transient activation of ERK in neighboring cells, preventing clustered cell elimination.