Hubrecht Institute, Utrecht, Netherlands.
Developmental Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
Science. 2024 Oct 11;386(6718):eadh1145. doi: 10.1126/science.adh1145.
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.
尽管生命系统具有内在的随机性，但它们如何在形态和功能上实现精确性，这是生物学中一个基本而持续的问题。我们生成了小鼠、兔和猴胚胎植入前胚胎发生的形态图谱，这些形态图谱显示，尽管卵裂球分裂被动地失步，但 8 细胞胚胎会向稳健的三维形状收敛。通过拓扑分析和遗传扰动，我们发现胚胎逐渐将其细胞连接性改变为优选拓扑，这可以通过一个物理模型来预测，该模型认为肌动球蛋白收缩和噪声有助于拓扑转变，从而降低表面能。这种机制有利于规则的胚胎包装，并促进在 16 细胞胚胎中有更多的内细胞。同步分裂减少了胚胎的包装，产生了更多的错位细胞和更少的内细胞团细胞。这些发现表明，分裂时间的随机性有助于稳健的模式形成。
