Morphogenesis of a stratified cell mound at a vortex defect

Abstract

Although topological defects in cell monolayers have been recognized as mechanical organizing centers in morphogenetic processes, the mechanism by which cells coordinate their motion at such defects and self-organize into higher-order structures remains elusive. Here, we report the formation of three-dimensional (3D) multicellular mounds in unconfined myoblast monolayers, at well-controlled vortex topological defects. Prior to the onset of bilayering, the vortex structure induces millimeter-scale cell flows converging toward the defect center. As a result, 3D cell mounds form at the defect core, layer-by-layer. These mounds grow by interlayer permeation sustained by the converging cell flows. At late stages, the bell shape of the structured mounds can be modeled with a dynamics driven by these converging flows. Our results therefore highlight the crucial role of integer topological defects in driving large-scale cell flows yielding the formation of highly ordered 3D tissues from a monolayer. We propose that similar mechanisms may be at play in certain morphogenetic and tumorigenic events.