Emergence of a prestressed eukaryotic nucleus during cellular differentiation and development
Emergence of a prestressed eukaryotic nucleus during cellular differentiation and development
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DOI：
10.1098/rsif.2010.0039.focus
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发表时间：
2010-06-06
影响因子：
3.9
通讯作者：
Shivashankar, G. V.
中科院分区：
文献类型：
--
作者：
Mazumder, Aprotim;Shivashankar, G. V.
核的形状和大小正在成为基因组功能的机械调节器。然而，染色质组装和各种核和细胞质支架之间的耦合知之甚少。目前的工作探讨了预应力核在各种细胞系统中的结构组织，从培养的细胞到生物体中的细胞。激光烧蚀和细胞扰动的组合用于破译核质接触的动态性质。在原代小鼠胚胎成纤维细胞中，异染色质结节的消融引起细胞核的各向异性收缩。肌动蛋白和微管的解聚以及肌球蛋白马达的抑制导致这些细胞质系统对细胞核施加的差异应力。核预应力的发病，然后映射在两个上下文中，第一，在胚胎干细胞的分化，预应力的签名出现与分化;第二，在生物体水平上，在早期果蝇胚胎细胞的细胞核或细胞质激光消融诱导细胞核的崩溃后，细胞化。因此，我们表明，桥接细胞核与细胞质的物理连接的相互作用决定了预应力真核细胞核的大小和形状。
Nuclear shape and size are emerging as mechanistic regulators of genome function. Yet, the coupling between chromatin assembly and various nuclear and cytoplasmic scaffolds is poorly understood. The present work explores the structural organization of a prestressed nucleus in a variety of cellular systems ranging from cells in culture to those in an organism. A combination of laser ablation and cellular perturbations was used to decipher the dynamic nature of the nucleo-cytoplasmic contacts. In primary mouse embryonic fibroblasts, ablation of heterochromatin nodes caused an anisotropic shrinkage of the nucleus. Depolymerization of actin and microtubules, and inhibition of myosin motors, resulted in the differential stresses that these cytoplasmic systems exert on the nucleus. The onset of nuclear prestress was then mapped in two contexts-first, in the differentiation of embryonic stem cells, where signatures of prestress appeared with differentiation; second, at an organism level, where nuclear or cytoplasmic laser ablations of cells in the early Drosophila embryo induced a collapse of the nucleus only after cellularization. We thus show that the interplay of physical connections bridging the nucleus with the cytoplasm governs the size and shape of a prestressed eukaryotic nucleus.