Physical constraints on early blastomere packings

Abstract At very early embryonic stages, when embryos are composed of just a few cells, establishing the correct packing arrangements (contacts) between cells is essential for the proper development of the organism. As early as the 4-cell stage, the observed cellular packings in different species are distinct and, in many cases, differ from the equilibrium packings expected for simple adherent and deformable particles. It is unclear what are the specific roles that different physical parameters, such as the forces between blastomeres, their division times, orientation of cell division and embryonic confinement, play in the control of these packing configurations. Here we simulate the non-equilibrium dynamics of cells in early embryos and systematically study how these different parameters affect embryonic packings at the 4-cell stage. In the absence of embryo confinement, we find that cellular packings are not robust, with multiple packing configurations simultaneously possible and very sensitive to parameter changes. Our results indicate that the geometry of the embryo confinement determines the packing configurations at the 4-cell stage, removing degeneracy in the possible packing configurations and overriding division rules in most cases. Overall, these results indicate that physical confinement of the embryo is essential to robustly specify proper cellular arrangements at very early developmental stages. Author summaryAt the initial stages of embryogenesis, the precise arrangement of cells in the embryo is critical to ensure that each cell gets the right chemical and physical signals to guide the formation of the organism. Even when the embryo is made of only four cells, different species feature varying cellular arrangements: cells in mouse embryos arrange as a tetrahedron, in the nematode worm C. elegans cells make a diamond and in sea urchins cells arrange in a square configuration. How do cells in embryos of different species control their arrangements? Using computer simulations, we studied how cell divisions, physical contacts between cells and the confinement of the embryo by an eggshell affect the arrangements of cells when the embryos have only 4 cells. We find that the shape of the confining eggshell plays a key role in controlling the cell arrangements, removing unwanted arrangements and robustly specifying the proper contacts between cells. Our results highlight the important roles of embryonic confinement in establishing the proper cell-cell contacts as the embryo starts to develop.