During preimplantation development, mouse embryos form a fluid-filled lumen. Pressurized fluid fractures cell–cell contacts and accumulates into pockets, which coarsen into a single lumen. How the embryo controls intercellular fluid movement during coarsening is unknown. We uncovered inverse blebs growing into cells at adhesive contacts as active excitable elements. Throughout the embryo we observed hundreds of inverse blebs, each filling with intercellular fluid and retracting within a minute. Inverse blebs grow due to pressure build-up resulting from fluid accumulation and cell–cell adhesion, which locally confines fluid. Inverse blebs retract due to actomyosin contraction, practically pushing fluid within the intercellular space. Importantly, inverse blebs occur infrequently at contacts formed by multiple cells, which effectively serve as fluid sinks. Manipulation of the embryo topology reveals that without sinks inverse blebs pump fluid into one another in futile cycles— delaying formation of the lumen. We propose that inverse blebs operate as excitable hydraulic pumps to promote luminal coarsening in a topology dependent manner, thereby linking geometric complexity of the embryo with timing of key developmental events.

Argo is a theoretical physicist and is drawn to biology by his fascination of natural forms. Argo’s research investigates, from the viewpoint of physics and applied geometry, how biophysical elements underlie cooperativity in morphogenesis at various scales, from cells to organs. During his graduate thesis as well as his independent tenure as a junior research chair in Paris, his work has spanned from studying how tissue hydraulics and mechanical instabilities influence cell fate decisions to examining topological principles governing morphogenesis. These examples have emphasized the role of theory driven exploration in living systems in obtaining fundamental insights and have given rise to not only key biological findings but also novel theoretical concepts and techniques.