After fertilization, sperm and oocyte nuclei are rapidly remodeled to form swollen pronuclei (PN) in mammalian zygotes, and the proper formation and function of PN are key to producing totipotent zygotes. However, how mature PN are formed has been unclear. We find that filamentous actin (F-actin) assembles in the PN of mouse zygotes and is required for fully functional PN. The perturbation of nuclear actin dynamics in zygotes results in the misregulation of genes related to genome integrity and abnormal development of mouse embryos. We show that nuclear F-actin ensures DNA damage repair, thus preventing the activation of a zygotic checkpoint. Furthermore, optogenetic control of cofilin nuclear localization reveals the dynamically regulated F-actin nucleoskeleton in zygotes, and its timely disassembly is needed for developmental progression. Nuclear F-actin is a hallmark of totipotent zygotic PN, and the temporal regulation of its polymerized state is necessary for normal embryonic development.

受精后，精子和卵母细胞核迅速重塑以形成哺乳动物合子中的膨大前核（PN），而PN的正确形成和功能是产生全能合子的关键。但是，尚不清楚PN如何形成。我们发现丝状肌动蛋白（F-肌动蛋白）组装在小鼠受精卵的PN和功能齐全的PN所需。受精卵中核肌动蛋白动力学的扰动导致与基因组完整性和小鼠胚胎发育异常有关的基因失调。我们表明，核F-肌动蛋白可确保DNA损伤修复，从而防止合子检查点的激活。此外，对cofilin核定位的光遗传学控制揭示了受精卵中动态调节的F-肌动蛋白核骨架，并且其及时拆卸对于发育进程是必需的。