Active Fluctuations of the Nuclear Envelope Shape the Transcriptional Dynamics in Oocytes
Active Fluctuations of the Nuclear Envelope Shape the Transcriptional Dynamics in Oocytes
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DOI：
10.1016/j.devcel.2019.09.010
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发表时间：
2019-10-21
影响因子：
11.8
通讯作者：
Verlhac, Marie-Helene
中科院分区：
文献类型：
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作者：
Almonacid, Maria;Al Jord, Adel;Verlhac, Marie-Helene
细胞核在细胞中的位置可以作为一种发育线索。哺乳动物卵母细胞使用F-肌动蛋白介导的压力梯度将其核定位在中央。哺乳动物卵母细胞核居中的生物学意义是未知的，我们试图评估F-肌动蛋白压力梯度对细胞核的影响。我们解决了这一问题，使用一个专门的计算三维成像方法，生物物理分析，并在小鼠卵母细胞突变细胞质F-肌动蛋白的细胞核重新定位测定。我们发现，细胞质的活动，负责核定中心，塑造了核，同时促进核膜的波动和染色质的运动。在F-肌动蛋白突变卵母细胞的偏离中心的细胞核与不动的染色质和调制的基因表达变形。突变卵母细胞中F-肌动蛋白的恢复完全挽救了核结构和部分基因表达。因此，F-肌动蛋白介导的压力梯度也调节卵母细胞的核动力学。此外，这项研究支持了一个机械转导模型，细胞质微丝可以调节卵母细胞转录组，为后续胚胎发育所必需的。
Nucleus position in cells can act as a developmental cue. Mammalian oocytes position their nucleus centrally using an F-actin-mediated pressure gradient. The biological significance of nucleus centering in mammalian oocytes being unknown, we sought to assess the F-actin pressure gradient effect on the nucleus. We addressed this using a dedicated computational 3D imaging approach, biophysical analyses, and a nucleus repositioning assay in mouse oocytes mutant for cytoplasmic F-actin. We found that the cytoplasmic activity, in charge of nucleus centering, shaped the nucleus while promoting nuclear envelope fluctuations and chromatin motion. Off-centered nuclei in F-actin mutant oocytes were misshaped with immobile chromatin and modulated gene expression. Restoration of F-actin in mutant oocytes rescued nucleus architecture fully and gene expression partially. Thus, the F-actin-mediated pressure gradient also modulates nucleus dynamics in oocytes. Moreover, this study supports a mechano-transduction model whereby cytoplasmic microfilaments could modulate oocyte transcriptome, essential for subsequent embryo development.