Inverse blebs operate as hydraulic pumps during mouse blastocyst formation

Abstract

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. Here we report inverse blebs growing into cells at adhesive contacts. 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. We propose that inverse blebs operate as hydraulic pumps to promote luminal coarsening, thereby constituting an instrument used by cells to control fluid movement.