Temporal variability and cell mechanics control robustness in mammalian embryogenesis

Science. 2024 Oct 11;386(6718):eadh1145. doi: 10.1126/science.adh1145. Epub 2024 Oct 11.

Abstract

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.

MeSH terms

  • Actomyosin / metabolism
  • Animals
  • Blastocyst / cytology
  • Blastocyst / physiology
  • Blastomeres* / cytology
  • Blastomeres* / physiology
  • Cell Division
  • Embryo, Mammalian* / cytology
  • Embryo, Mammalian* / physiology
  • Embryonic Development*
  • Mice
  • Rabbits
  • Stochastic Processes

Substances

  • Actomyosin