As cytoskeletal motors remodel the cytoplasm, their activity generates forces that act on organelles and the contents of the nucleus. In developing mammalian oocytes, cytoplasmic remodeling by F-actin and myosin positions the nucleus at the cell center, ensuring successful development and embryogenic potential. However, the functional effects of this cytoplasmic remodeling on nuclear condensates are unclear. By observing the merging of nucleoli during cytoplasmic remodeling in mouse oocytes, Al Jord et al. investigated whether cytoplasmic forces affect the organization of nuclear condensates. They first developed a classification system for oocytes at the late-growth stage based on cytoplasmic stirring intensity and nucleus position. Initial analysis focusing on liquid-like condensates in control and F-actin-mutant (Fmn2−/−) oocytes showed nuclear condensate droplets coalescing (decreasing in number while increasing in size) through the development stages in control but not mutant oocytes. Live imaging of cells in varying experimental conditions revealed droplet displacement and fusion caused by nuclear membrane fluctuation — supported by droplet diffusion correlating with nuclear agitation — which confirms the role of cytoplasmic forces in enhancing droplet coalescence. The authors built a computational model to reproduce control and modulated droplet activity. This model demonstrated the predominant role of cytoplasmic forces in driving droplet coalescence to achieve nuclear condensate organization observed in the final growth stage of oocytes. Molecular dynamics in droplets and immunostaining for catalytically active spliceosomes also suggested a role for cytoplasmic forces in sustaining spliceosome activity inside nuclear droplets, and the authors linked this spliceosome activity to the processing of maternal mRNA and successful oocyte meiosis. Finally, they demonstrated evolutionary conservation of their findings, which were also seen in Drosophila melanogaster oocytes. These results have the potential to inform future work on in vitro fertilization and oocyte nucleus transfer, as well as shedding light on a physical mechanism that is potentially relevant across other cell types and in diseases.
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