UC Santa Barbara

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 proper development of the organism. As early as the 4-cell stage, the observed blastomere packings in different species are different and, in many cases, differ from the equilibrium packings expected for simple adherent and deformable particles.

We use a novel 3D Voronoi-augnemted Langevin simulator to systematically study how the forces between blastomeres, their division rates, orientation of cell division, and embryonic confinement influence the final packing configurations. In the absence of physical confinement of the embryo, we find that blastomere packings are not robust, with multiple packing configurations simultaneously possible (degeneracy) and are very sensitive to parameter changes. Our results indicate that the geometry of the embryonic confining shell determines the packing configurations at the 4-cell stage, removing degeneracy in the possible packing configurations and overriding division rules in most cases.

Furthermore, we use our simulator to study the robustness of the C. elegans early embryo to noise in division timing and angle. We find that there exists a range of timing and angular noise that the embryo is fully robust to and categorize the errors outside this regime as coming from mistimed divisions or misplaced cells. We also study how robust the embryo is to overall shifts in the timing offset between the AB and P1 divisions and find that even large changes can be non-lethal. Finally, we systematically investigate how robust the embryo is to deterministic shifts in division directions from the wildtype rules and find that the major source of lethal error is from offsets of more than 90 degrees to the P2-EMS division axis. Overall, our results demonstrate how confinement, division timing and division rules all contribute to ensuring robust development with confinement setting the overall packing topology and division timings and rules specifying where individual cells will go within that shape.