Geometry-driven asymmetric cell divisions pattern cell cycles and zygotic genome activation in the zebrafish embryo

Embryo geometry is one of the most consistent traits of a species, suggesting that it may serve as a foundational principle for developmental reproducibility and robustness. Here, we show that the zebrafish zygote geometry directs asymmetric cell divisions in the forming blastoderm, establishing radial gradients of cell volume and, consequently, the nucleocytoplasmic ratio. These gradients organize cell divisions along mitotic phase waves, with individual cell periods determined cell autonomously by the nucleocytoplasmic ratio. Remarkably, we found that this geometry-generated cell volume gradient not only instructs mitotic waves but also spatially patterns zygotic genome activation (ZGA) during the midblastula transition. Thus, our study reveals a novel symmetry-breaking function of early embryo geometry in cell cycle and ZGA patterning, establishing the blueprint for further embryonic development.