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核变形性促进斑马鱼视网膜发育过程中的细胞核顶端迁移。

Nuclear deformability facilitates apical nuclear migration in the developing zebrafish retina.

作者信息

Maia-Gil Mariana, Gorjão Maria, Belousov Roman, Espina Jaime A, Coelho João, Gouhier Juliette, Ramos Ana P, Barriga Elias H, Erzberger Anna, Norden Caren

机构信息

Gulbenkian Institute for Molecular Medicine (GIMM) (previously Instituto Gulbenkian de Ciência), Rua da Quinta Grande 6, 2780-156 Oeiras, Portugal.

Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.

出版信息

Curr Biol. 2024 Dec 2;34(23):5429-5443.e8. doi: 10.1016/j.cub.2024.10.015. Epub 2024 Oct 30.

Abstract

Nuclear positioning is a crucial aspect of cell and developmental biology. One example is the apical movement of nuclei in neuroepithelia before mitosis, which is essential for proper tissue formation. While the cytoskeletal mechanisms that drive nuclei to the apical side have been explored, the influence of nuclear properties on apical nuclear migration is less understood. Nuclear properties, such as deformability, can be linked to lamin A/C expression levels, as shown in various in vitro studies. Interestingly, many nuclei in early development, including neuroepithelial nuclei, express only low levels of lamin A/C. Therefore, we investigated whether increased lamin A expression in the densely packed zebrafish retinal neuroepithelium affects nuclear deformability and, consequently, migration phenomena. We found that overexpressing lamin A in retinal nuclei increases nuclear stiffness, which in turn indeed impairs apical nuclear migration. Interestingly, nuclei that do not overexpress lamin A but are embedded in a stiffer lamin A-overexpressing environment also exhibit impaired apical nuclear migration, indicating that these effects can be cell non-autonomous. Additionally, in the less crowded hindbrain neuroepithelium, only minor effects on apical nuclear migration are observed. Together, this suggests that the material properties of the nucleus influence nuclear movements in a tissue-dependent manner.

摘要

细胞核定位是细胞生物学和发育生物学的一个关键方面。一个例子是有丝分裂前神经上皮细胞核的顶端移动,这对正常组织形成至关重要。虽然驱动细胞核向顶端移动的细胞骨架机制已被探索,但细胞核特性对顶端核迁移的影响却知之甚少。如各种体外研究所示,细胞核特性,如可变形性,可能与核纤层蛋白A/C的表达水平有关。有趣的是,在早期发育中的许多细胞核,包括神经上皮细胞核,仅表达低水平的核纤层蛋白A/C。因此,我们研究了在紧密排列的斑马鱼视网膜神经上皮中增加核纤层蛋白A的表达是否会影响细胞核的可变形性,进而影响迁移现象。我们发现,在视网膜细胞核中过表达核纤层蛋白A会增加细胞核硬度,这反过来确实会损害顶端核迁移。有趣的是,未过表达核纤层蛋白A但嵌入在更硬的过表达核纤层蛋白A环境中的细胞核也表现出顶端核迁移受损,这表明这些影响可能是非细胞自主性的。此外,在不太拥挤的后脑神经上皮中,仅观察到对顶端核迁移的轻微影响。总之,这表明细胞核的物质特性以组织依赖的方式影响核运动。

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