Compressive stress drives morphogenetic apoptosis through lateral tension and Piezo1

Tissues and organs are constantly submitted to physical stress, including compression, stretching, shear stress. The impact of compression due to overcrowding on cell extrusion has been the focus of recent studies. However, how tissue compression impact cell death in the context of morphogenesis is mostly unexplored. Here, we showed that a natural compression is exerted on the Drosophila developing leg by the surrounding tissue (or envelope) that is required for correct leg morphogenesis. In this tissue, apoptosis, preferentially localized in the future fold region, contributes to drive tissue folding through the generation of a pulling force on the apical surface. However, only a subset of these cells are dying within the expression domain of proapoptotic genes and how this precise pattern of cell death is established is totally unknown. We found that the natural compression exerted by the envelope contributes to the regulation of apoptosis, revealing that compression constitutes an integral part of apoptosis regulation during leg morphogenesis. We further reveal that compression drives a significant increase in lateral tension and favors apoptosis through the mechanosensor Piezo. Finally, perturbing cell cortex anchoring or membrane stiffness prove sufficient to block this process. Altogether, these results open new perspectives in term of mechanotransduction during morphogenesis.