Apico-basal forces exerted by apoptotic cells drive epithelium folding

Apoptotic cell death is required for morphogenesis of the developing leg joint of fruitflies; using this model system, the authors show here that within apoptotic cells a transient pulling force exerted through a highly dynamic apico-basal myosin II cable-like structure acts as a mechanical signal to increase tissue tension and modify tissue shape. Apoptosis involved in tissue folding During animal development, epithelial tissues fold into highly organized three-dimensional structures in a process that involves cell-autonomous reorganization of the cytoskeleton and cellular junctions. But what are the signals that trigger and coordinate cell remodelling required for proper folding? Magali Suzanne and colleagues previously reported that a pattern of apoptotic cell death is required for joint formation in the developing leg of adult fruitflies. Using the same model system, the authors now show that a transient pulling force through a highly dynamic apico-basal myosin II 'cable' within these apoptotic cells acts as a mechanical signal to increase tissue tension. Together with stabilization of cortical myosin II in the surrounding tissue, this instructs the reorganization of neighbouring cells and so epithelium folding. The active role of apoptotic cells in development is an intriguing finding. Epithelium folding is a basic morphogenetic event that is essential in transforming simple two-dimensional epithelial sheets into three-dimensional structures in both vertebrates and invertebrates 1 . Folding has been shown to rely on apical constriction 2 , 3 , 4 , 5 , 6 , 7 . The resulting cell-shape changes depend either on adherens junction basal shift 2 or on a redistribution of myosin II 3 , 4 , 5 , 7 , which could be driven by mechanical signals 8 . Yet the initial cellular mechanisms that trigger and coordinate cell remodelling remain largely unknown. Here we unravel the active role of apoptotic cells in initiating morphogenesis, thus revealing a novel mechanism of epithelium folding. We show that, in a live developing tissue, apoptotic cells exert a transient pulling force upon the apical surface of the epithelium through a highly dynamic apico-basal myosin II cable. The apoptotic cells then induce a non-autonomous increase in tissue tension together with cortical myosin II apical stabilization in the surrounding tissue, eventually resulting in epithelium folding. Together our results, supported by a theoretical biophysical three-dimensional model, identify an