Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Max Planck Institute for the Physics of Complex Systems, Dresden, Germany.
J Cell Biol. 2019 Oct 7;218(10):3272-3289. doi: 10.1083/jcb.201901077. Epub 2019 Aug 16.
Correct nuclear position is crucial for cellular function and tissue development. Depending on cell context, however, the cytoskeletal elements responsible for nuclear positioning vary. While these cytoskeletal mechanisms have been intensely studied in single cells, how nuclear positioning is linked to tissue morphology is less clear. Here, we compare apical nuclear positioning in zebrafish neuroepithelia. We find that kinetics and actin-dependent mechanisms of nuclear positioning vary in tissues of different morphology. In straight neuroepithelia, nuclear positioning is controlled by Rho-ROCK-dependent myosin contractility. In contrast, in basally constricted neuroepithelia, a novel formin-dependent pushing mechanism is found for which we propose a proof-of-principle force generation theory. Overall, our data suggest that correct nuclear positioning is ensured by the adaptability of the cytoskeleton to cell and tissue shape. This in turn leads to robust epithelial maturation across geometries. The conclusion that different nuclear positioning mechanisms are favored in tissues of different morphology highlights the importance of developmental context for the execution of intracellular processes.
正确的核定位对于细胞功能和组织发育至关重要。然而,根据细胞的上下文,负责核定位的细胞骨架元素有所不同。虽然这些细胞骨架机制在单细胞中得到了深入研究,但核定位如何与组织形态相关联还不太清楚。在这里,我们比较了斑马鱼神经上皮的顶端核定位。我们发现,在形态不同的组织中,核定位的动力学和肌动蛋白依赖性机制存在差异。在直的神经上皮中,核定位受 Rho-ROCK 依赖性肌球蛋白收缩的控制。相比之下,在基底受限的神经上皮中,发现了一种新型的formin 依赖性推动机制,我们为此提出了一个原理证明的力产生理论。总的来说,我们的数据表明,核定位的准确性是由细胞骨架对细胞和组织形状的适应性来保证的。这反过来又导致了在不同几何形状下上皮成熟的稳健性。不同的核定位机制在形态不同的组织中更受欢迎的结论强调了发育背景对于细胞内过程执行的重要性。