Development is in large part driven by mechanics, but our understanding of the underlying mechanisms is largely incomplete. Chan et al. now show that hydraulic forces have important roles in the early development of mouse embryos.

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The mammalian blastocyst comprises a fluid-filled cavity (blastocoel) and two cell lineages: trophectoderm, which forms an outer layer and generates extra-embryonic tissues, and the inner cell mass (ICM), which gives rise to the embryo proper. The authors demonstrated that when the blastocyst forms, the blastocoel initially expands in volume until it reaches a steady state characterized by cycles of collapse and re-expansion without further growth. The increase in blastocoel volume was accompanied by a build-up of pressure in the blastocoel and increase in trophectoderm stiffness. This stiffening in turn was associated with cell stretching and increased cortical tension, which was coupled with cytoskeletal remodelling and maturation of tight junctions. Changes in the blastocoel volume led to equivalent changes in trophectoderm cell cortical tension, but when measured at steady state, cortical tension was comparable in mature blastocysts of various sizes, suggesting that hydraulically generated cortical tension sets the threshold for blastocyst size.

The authors next showed that the build-up of tension in the trophectoderm eventually compromises the stability of cell junctions upon entry into mitosis of the trophectoderm cells. This was associated with junction leakiness, fluid efflux from the blastocoel and blastocyst collapse, which could be promoted or suppressed — thereby regulating blastocyst size — by increasing or decreasing cellular contractility, respectively. Thus, interplay between blastocoel volume expansion and concomitant increase in trophectoderm cortical tension regulates the size of the blastocyst.

hydraulically generated cortical tension sets the threshold for blastocyst size

Finally, in embryos with smaller cavities, ICM-to-trophectoderm cell ratio was increased; the opposite effect was observed when blastocoels were expanded. This suggests that mechanics of the early embryo — based on the regulation of hydraulic pressure in the blastocoel — have a large impact on early mammalian development, including the regulation of blastocyst size and the first cell-fate decisions in the embryo.