Developmental and Stem Cell Biology Department, Institut Pasteur, Université de Paris, CNRS UMR3738, Paris, France.
Collège Doctoral, Sorbonne Université, Paris, France.
Nature. 2024 Sep;633(8031):887-894. doi: 10.1038/s41586-024-07934-8. Epub 2024 Sep 11.
Early amniote development is highly self-organized, capable of adapting to interference through local and long-range cell-cell interactions. This process, called embryonic regulation, has been well illustrated in experiments on avian embryos, in which subdividing the epiblast disk into different parts not only redirects cell fates to eventually form a complete and well-proportioned embryo at its original location, but also leads to the self-organization of additional, fully formed embryos in the other separated parts. The cellular interactions underlying embryonic self-organization are widely believed to be mediated by molecular signals, yet the identity of such signals is unclear. Here, by analysing intact and mechanically perturbed quail embryos, we show that the mechanical forces that drive embryogenesis self-organize, with contractility locally self-activating and the ensuing tension acting as a long-range inhibitor. This mechanical feedback governs the persistent pattern of tissue flows that shape the embryo and also steers the concomitant emergence of embryonic territories by modulating gene expression, ensuring the formation of a single embryo under normal conditions, yet allowing the emergence of multiple, well-proportioned embryos after perturbations. Thus, mechanical forces act at the core of embryonic self-organization, shaping both tissues and gene expression to robustly yet plastically canalize early development.
早期羊膜动物的发育具有高度的自我组织能力,能够通过局部和远程细胞间的相互作用适应干扰。这个过程被称为胚胎调控,在鸟类胚胎实验中得到了很好的说明,在这些实验中,将外胚层盘分割成不同的部分,不仅会改变细胞命运,最终在原始位置形成一个完整且比例协调的胚胎,还会导致额外的、完全形成的胚胎在其他分离的部分中自我组织。人们普遍认为,胚胎自我组织的细胞间相互作用是由分子信号介导的,但这些信号的身份尚不清楚。在这里,通过分析完整的和机械扰动的鹌鹑胚胎,我们表明,驱动胚胎发生自我组织的机械力是通过收缩性局部自我激活和随之产生的张力作为远程抑制剂来实现的。这种机械反馈控制着塑造胚胎的组织流的持续模式,通过调节基因表达来引导胚胎区域的同时出现,确保在正常条件下形成单个胚胎,但允许在扰动后出现多个比例协调的胚胎。因此,机械力是胚胎自我组织的核心,塑造组织和基因表达,以强大而灵活的方式对早期发育进行渠道化。