Integrins coordinate basal surface contraction and oriented cell growth to enable thickening of a curved epithelium.

Abstract

During development, tissues undergo morphogenesis to achieve their final form. This process relies on coordinated cell shape changes, which have predominantly been studied in one plane, at the apical (top) surface of developing tissues. However, tissues are three dimensional, often exhibiting deformations along multiple axes. To understand how morphogenesis is coordinated across tissue axes, we used the genetically amenable Drosophila retina, a curved, dome-shaped epithelium, as a model system. Using intravital imaging, we found that retinal curvature is induced early in development. Modeling early retinal development with a vertex model suggests that this curvature arises from differential planar growth between the apical and basal tissue surfaces. In addition, mechanical perturbation experiments revealed that inside-out fluid pressure plays a crucial role in promoting this curvature. Further combining computational modeling, genetic perturbations, and force-inference experiments, we demonstrate that uniform thickening of the curved retinal epithelium requires coordination of two key processes: growth, promoting cell elongation along the apical-basal axis of the tissue, and basal surface contraction. Remarkably, inhibiting basal surface contraction-both in silico and through genetic manipulations targeting the basal surface receptor integrin and non-muscle myosin-II-prevented cell elongation. We conclude that thickening of a curved epithelium, like the Drosophila retina, requires both integrin and non-muscle myosin-II to coordinate basal surface contraction and cell growth along the apical-basal axis of the tissue.