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Tissue Mechanics Regulate Mitotic Nuclear Dynamics during Epithelial Development.
Current Biology ( IF 8.1 ) Pub Date : 2020-05-14 , DOI: 10.1016/j.cub.2020.04.041
Natalie J Kirkland 1 , Alice C Yuen 2 , Melda Tozluoglu 1 , Nancy Hui 1 , Ewa K Paluch 3 , Yanlan Mao 4
Affiliation  

Cell divisions are essential for tissue growth. In pseudostratified epithelia, where nuclei are staggered across the tissue, each nucleus migrates apically before undergoing mitosis. Successful apical nuclear migration is critical for planar-orientated cell divisions in densely packed epithelia. Most previous investigations have focused on the local cellular mechanisms controlling nuclear migration. Inter-species and inter-organ comparisons of different pseudostratified epithelia suggest global tissue architecture may influence nuclear dynamics, but the underlying mechanisms remain elusive. Here, we use the developing Drosophila wing disc to systematically investigate, in a single epithelial type, how changes in tissue architecture during growth influence mitotic nuclear migration. We observe distinct nuclear dynamics at discrete developmental stages, as epithelial morphology changes. We use genetic and physical perturbations to show a direct effect of cell density on mitotic nuclear positioning. We find Rho kinase and Diaphanous, which facilitate mitotic cell rounding in confined cell conditions, are essential for efficient apical nuclear movement. Perturbation of Diaphanous causes increasing defects in apical nuclear migration as the tissue grows and cell density increases, and these defects can be reversed by acute physical reduction of cell density. Our findings reveal how the mechanical environment imposed on cells within a tissue alters the molecular and cellular mechanisms adopted by single cells for mitosis.



中文翻译:

组织力学在上皮发育过程中调节有丝分裂核动力学。

细胞分裂对组织生长至关重要。在假复层上皮细胞中,细胞核在组织中交错排列,每个细胞核在进行有丝分裂之前都会向顶端迁移。成功的顶端核迁移对于密集上皮细胞中的平面定向细胞分裂至关重要。大多数先前的研究都集中在控制核迁移的局部细胞机制上。不同假复层上皮的物种间和器官间比较表明,整体组织结构可能会影响核动力学,但潜在的机制仍然难以捉摸。在这里,我们使用正在发展的果蝇翼盘系统地研究,在单一上皮类型中,生长过程中组织结构的变化如何影响有丝分裂核迁移。随着上皮形态的变化,我们在离散的发育阶段观察到不同的核动力学。我们使用遗传和物理扰动来显示细胞密度对有丝分裂核定位的直接影响。我们发现在受限细胞条件下促进有丝分裂细胞变圆的 Rho 激酶和 Diaphanous 对有效的顶端核运动至关重要。随着组织的生长和细胞密度的增加,Diaphanous 的扰动导致顶端核迁移的缺陷增加,并且这些缺陷可以通过细胞密度的急性物理降低来逆转。

更新日期:2020-07-06
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