Piezo regulates epithelial topology and promotes precision in organ size control.

Mechanosensitive Piezo channels regulate cell division, cell extrusion, and cell death. However, systems-level functions of Piezo in regulating organogenesis remain poorly understood. Here, we demonstrate that Piezo controls epithelial cell topology to ensure precise organ growth by integrating live-imaging experiments with pharmacological and genetic perturbations and computational modeling. Notably, the knockout or knockdown of Piezo increases bilateral asymmetry in wing size. Piezo's multifaceted functions can be deconstructed as either autonomous or non-autonomous based on a comparison between tissue-compartment-level perturbations or between genetic perturbation populations at the whole-tissue level. A computational model that posits cell proliferation and apoptosis regulation through modulation of the cutoff tension required for Piezo channel activation explains key cell and tissue phenotypes arising from perturbations of Piezo expression levels. Our findings demonstrate that Piezo promotes robustness in regulating epithelial topology and is necessary for precise organ size control.