Embryo mechanics cartography: inference of 3D force atlases from fluorescence microscopy

Abstract

AbstractTissue morphogenesis results from a tight interplay between gene expression, biochemical signaling and mechanics. Although sequencing methods allow the generation of cell-resolved spatiotemporal maps of gene expression, creating similar maps of cell mechanics in three-dimensional (3D) developing tissues has remained a real challenge. Exploiting the foam-like arrangement of cells, we propose a robust end-to-end computational method called ‘foambryo’ to infer spatiotemporal atlases of cellular forces from fluorescence microscopy images of cell membranes. Our method generates precise 3D meshes of cells’ geometry and successively predicts relative cell surface tensions and pressures. We validate it with 3D foam simulations, study its noise sensitivity and prove its biological relevance in mouse, ascidian and worm embryos. 3D force inference allows us to recover mechanical features identified previously, but also predicts new ones, unveiling potential new insights on the spatiotemporal regulation of cell mechanics in developing embryos. Our code is freely available and paves the way for unraveling the unknown mechanochemical feedbacks that control embryo and tissue morphogenesis.