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Zygotic Nuclear F-Actin Safeguards Embryonic Development

2020; Cell Press; Volume: 31; Issue: 13 Linguagem: Inglês

10.1016/j.celrep.2020.107824

2639-1856

Tomomi Okuno, Wayne Yang Li, Yu Hatano, Atsushi Takasu, Yuko Sakamoto, Mari Yamamoto, Zenki Ikeda, Taiki Shindo, Matthias Plessner, Kohtaro Morita, Kazuya Matsumoto, Kazuo Yamagata, Robert Grosse, Kei Miyamoto,

Pluripotent Stem Cells Research

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.