Temporal variability and cell mechanics control robustness in mammalian embryogenesis

• 成果类型: Article
• 署名作者: Fabreges, Dimitri; Corominas-Murtra, Bernat; Moghe, Prachiti; Kickuth, Alison; Ichikawa, Takafumi; Iwatani, Chizuru; Tsukiyama, Tomoyuki; Daniel, Nathalie; Gering, Julie; Stokkermans, Anniek; Wolny, Adrian; Kreshuk, Anna; Duranthon, Veronique; Uhlman, Virginie; Hannezo, Edouard; Hiiragi, Takashi
• 署名单位: Royal Netherlands Academy of Arts & Sciences; Hubrecht Institute (KNAW); European Molecular Biology Laboratory (EMBL); University of Graz; Kyoto University; Kyoto University; Shiga University of Medical Science; INRAE; Universite Paris Saclay; European Molecular Biology Laboratory (EMBL); Universite Paris Saclay; Ecole Nationale Veterinaire d'Alfort (ENVA); European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; Institute of Science & Technology - Austria; Technische Universitat Dresden; Max Planck Society; University of Zurich
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-10157
• DOI: 10.1126/science.adh1145
• 发表日期: 2024-10-01
• 关键词: gene-expression; in-vitro; mouse; division; noise; embryos; cleavage; GROWTH; fate; CLASSIFICATION

摘要

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.