Local weakening of cell-ECM adhesion triggers basal tissue folding via changes in cell shape, actomyosin organization and E-cad levels

During development, epithelial sheets sculpt organs by folding, either apically or basally, into complex 3D structures. Given the presence of actomyosin networks and cell adhesion sites on both sides of cells, a common machinery mediating apical and basal epithelial tissue folding has been proposed. However, little is known about the mechanisms regulating epithelial folding towards the basal side. Here, using the Drosophila wing imaginal disc and a multidisciplinary approach, combining genetic perturbations and computational modelling, we demonstrate opposing roles for cell-cell and cell-ECM adhesion systems during epithelial folding. Thus, while cadherin-mediated adhesion, linked to actomyosin network, regulates apical folding, a reduction on integrin-dependent adhesion, followed by changes in cell shape, organization of the basal actomyosin cytoskeleton and E-Cad levels, is necessary and sufficient to trigger basal folding. These results suggest that modulation of the cell mechanical landscape through the crosstalk between integrins and cadherins is essential for correct epithelial folding.