From genes to geometry: how biology uses physics to sculpt an organ

Abstract: In morphogenesis, tissues integrate mechanical and biochemical signals to direct organ-scale geometric transformations. Uncovering the dynamic interplay between genetic patterning, mechanical forces, and tissue geometry requires a physical understanding of how cell interactions collectively deform the composite tissue. A broad class of organs, including the gut and heart, form from tube-like sheets of multiple cell layers that fold, bend, and stretch into complex shapes. Specific genes have long been known to regulate organ shape, but the underlying physics remains mysterious. How do gene expression, active stress, and tissue elasticity interact to drive organ shape transformations? Here, we trace the dynamics and mechanical interactions driving organ folding, using the embryonic midgut of the fruit fly as a model system. We capture dynamics of the entire organ with cellular resolution using advanced imaging techniques. By extracting cell and tissue deformations within morphing 3D geometries, we then reveal the kinematic mechanism linking in-plane and out-of-plane deformations. Merging this approach with molecular perturbations uncovers a multi-scale mechanical program acting across tissue layers. This work establishes a quantitative approach for decoding how active forces in sheets of interacting cells generate complex 3D organ geometries.