Optic cup folding is driven by the geometry and tension of the Retinal Pigmented Epithelium (RPE) cells

Abstract

While optic cup folding is known to involve specific geometrical changes of RPE cells, the precise gene regulatory mechanisms orchestrating the adoption of their highly rigid geometry, and how these contribute to successful folding, remain poorly understood. To address this gap, we investigated how the increase in mechanical tension and maintenance of an elongated geometry depend on the activation of the Wnt/{beta}-catenin and YAP pathways in RPE cells. We demonstrated that interference with these pathways causes folding failure due to a reduction in RPE cellular tension. We also identified transcriptional programs controlled by these pathways that regulate the mechanical properties of the actin cytoskeleton, cell-to-cell and cell-to-ECM adhesions, and endocytosis. Finally, we hypothesized that the LINC complex, which transmits tension between the cell and nuclear membranes, is responsible for the nuclear entry of {beta}-catenin and YAP in a cellular geometry-dependent manner. We combined quantitative imaging, functional analysis, mechanical perturbation assays, and transcriptomic analysis to generate a comprehensive view of how the coordination of mechanosensitive gene expression and changes in cellular geometries drive eye formation.