近日，奥地利科学技术研究所Heisenberg, Carl-Philipp团队报道了几何驱动的非对称细胞分裂模式细胞周期和斑马鱼胚胎中的合子基因组激活。相关论文发表在2026年1月5日出版的《自然—物理学》杂志上。
早期胚胎的几何形态是最具物种特异性的不变特征之一，然而，它在确保发育可重复性和稳健性方面的作用尚未得到充分探索。
研究组表明，在斑马鱼中，受精卵的几何形态——特别是其曲率和体积——是触发一系列影响发育事件的至关重要的初始条件。胚胎几何形态引导囊胚层中模式化的不对称细胞分裂，产生细胞体积和核质比的径向梯度。这些梯度产生有丝分裂相波，其中核质比独立于其他细胞，决定着单个细胞的周期周期。
研究组证明，降低细胞自主性会重塑这些波，强调了由几何形态衍生的体积模式在设定细胞周期振荡器固有周期中的指导作用。除了组织细胞周期外，早期胚胎的几何形态还在中囊胚转变时对合子基因组的激活进行空间模式化，这是建立胚胎自主性的关键步骤。破坏胚胎形状会改变合子基因组的激活模式，并导致胚层的异位特化，凸显了几何形态在发育中的重要性。综上所述，该发现揭示了早期胚胎几何形态在协调细胞周期和转录模式化中的对称性破坏功能。
附：英文原文
Title: Geometry-driven asymmetric cell divisions pattern cell cycles and zygotic genome activation in the zebrafish embryo
Author: Mishra, Nikhil, Li, Yuting Irene, Hannezo, Edouard, Heisenberg, Carl-Philipp
Issue&Volume: 2026-01-05
Abstract: Early embryo geometry is one of the most invariant species-specific traits, yet its role in ensuring developmental reproducibility and robustness remains underexplored. Here we show that in zebrafish, the geometry of the fertilized egg—specifically its curvature and volume—serves as a critical initial condition triggering a cascade of events that influence development. The embryo geometry guides patterned asymmetric cell divisions in the blastoderm, generating radial gradients of cell volume and nucleocytoplasmic ratio. These gradients generate mitotic phase waves, with the nucleocytoplasmic ratio determining individual cell cycle periods independently of other cells. We demonstrate that reducing cell autonomy reshapes these waves, emphasizing the instructive role of geometry-derived volume patterns in setting the intrinsic period of the cell cycle oscillator. In addition to organizing cell cycles, early embryo geometry spatially patterns zygotic genome activation at the midblastula transition, a key step in establishing embryonic autonomy. Disrupting the embryo shape alters the zygotic genome activation pattern and causes ectopic germ layer specification, underscoring the developmental significance of geometry. Together, our findings reveal a symmetry-breaking function of early embryo geometry in coordinating cell cycle and transcriptional patterning.
DOI: 10.1038/s41567-025-03122-1
Source: https://www.nature.com/articles/s41567-025-03122-1