Temporal variability and cell mechanics control robustness in mammalian embryogenesis Fabrèges, Dimitri Corominas-Murtra, Bernat ; https://orcid.org/0000-0001-9806-5643 Moghe, Prachiti Kickuth, Alison Ichikawa, Takafumi Iwatani, Chizuru Tsukiyama, Tomoyuki Daniel, Nathalie Gering, Julie Stokkermans, Anniek Wolny, Adrian Kreshuk, Anna Duranthon, Véronique Uhlman, Virginie Hannezo, Edouard B ; https://orcid.org/0000-0001-6005-1561 Hiiragi, Takashi How living systems achieve precision in form and function despite their intrinsic stochasticity is a fundamental yet ongoing question in biology. We generated morphomaps of preimplantation embryogenesis in mouse, rabbit, and monkey embryos, and these morphomaps revealed that although blastomere divisions desynchronized passively, 8-cell embryos converged toward robust three-dimensional shapes. Using topological analysis and genetic perturbations, we found that embryos progressively changed their cellular connectivity to a preferred topology, which could be predicted by a physical model in which actomyosin contractility and noise facilitate topological transitions, lowering surface energy. This mechanism favored regular embryo packing and promoted a higher number of inner cells in the 16-cell embryo. Synchronized division reduced embryo packing and generated substantially more misallocated cells and fewer inner-cell–mass cells. These findings suggest that stochasticity in division timing contributes to robust patterning. AAAS 2024 info:eu-repo/semantics/article doc-type:Article Article http://purl.org/coar/resource_type/c_2df8fbb1 https://research-explorer.ista.ac.at/record/18446 Fabrèges D, Corominas-Murtra B, Moghe P, et al. Temporal variability and cell mechanics control robustness in mammalian embryogenesis. <i>Science</i>. 2024;386(6718). doi:<a href="https://doi.org/10.1126/science.adh1145">10.1126/science.adh1145</a> eng info:eu-repo/semantics/altIdentifier/doi/10.1126/science.adh1145 info:eu-repo/semantics/altIdentifier/e-issn/1095-9203 info:eu-repo/semantics/altIdentifier/wos/001422132300018 info:eu-repo/semantics/altIdentifier/pmid/39388574 info:eu-repo/semantics/openAccess