Compressive stress drives morphogenetic apoptosis

Abstract

AbstractTissues and organs are constantly submitted to physical stress, including compression, stretching, shear stress. These physical constraints can influence fundamental processes such cell division, cell death and cell differentiation. In particular, the impact of compression due to overproliferation and overcrowding has been the focus of a number of recent studies, revealing the importance of mechanics in the regulation of cell number and tissue homeostasis. However, addressing the impact of mechanical challenges in living organisms remains a challenge and how tissue compression impact cell death in the context of morphogenesis is totally unknown. Here we address this question using the drosophila leg disc as a model system. In this model, we showed that a natural compression is exerted by the surrounding tissue or envelope and that this compression is required for the correct morphogenesis of the underlying tissue, the developing leg. In this tissue, apoptosis contributes to the change in tissue shape through the generation of a pulling force on the apical surface. Apoptosis is preferentially localized in the future fold region, induced by the expression of proapoptotic genes. However, only a subset of cells expressing the proapoptotic genes are dying and how this precise pattern of cell death is established is totally unknown. Here, we found that the natural compression exerted by the envelope contributes to the precise regulation of apoptosis, the absence of compression reducing drastically the number of apoptotic events while the presence of high compression increases the number of dying cells. Thus, compression constitutes an integral part of apoptosis regulation during leg morphogenesis. We analyzed the consequences of compression on cell and nuclear geometry and found that compression affects mainly cell anisotropy and nucleus aspect ratio. We further decipher subcellular tension redistribution under compressive stress and revealed an important switch in lateral tension and opening new perspectives in term of mechanotransduction.