Biological Physics and Morphogenesis Group, Max Planck Institute for Dynamics and Self-Organization, Göttingen, Germany.
Institute for Developmental Biochemistry, Medical School, University of Göttingen, Göttingen, Germany.
Biophys J. 2018 Apr 10;114(7):1730-1740. doi: 10.1016/j.bpj.2018.02.018.
During the initial development of syncytial embryos, nuclei go through cycles of nuclear division and spatial rearrangement. The arising spatial pattern of nuclei is important for subsequent cellularization and morphing of the embryo. Although nuclei are contained within a common cytoplasm, cytoskeletal proteins are nonuniformly packaged into regions around every nucleus. In fact, cytoskeletal elements like microtubules and their associated motor proteins exert stochastic forces between nuclei, actively driving their rearrangement. Yet, it is unknown how the stochastic forces are balanced to maintain nuclear order in light of increased nuclear density upon every round of divisions. Here, we investigate the nuclear arrangements in Drosophila melanogaster over the course of several nuclear divisions starting from interphase 11. We develop a theoretical model in which we distinguish long-ranged passive forces due to the nuclei as inclusions in the elastic matrix, namely the cytoplasm, and active, stochastic forces arising from the cytoskeletal dynamics mediated by motor proteins. We perform computer simulations and quantify the observed degree of orientational and spatial order of nuclei. Solely doubling the nuclear density upon nuclear division, the model predicts a decrease in nuclear order. Comparing results to experimental recordings of tracked nuclei, we make contradictory observations, finding an increase in nuclear order upon nuclear divisions. Our analysis of model parameters resulting from this comparison suggests that overall motor protein density as well as relative active-force amplitude has to decrease by a factor of about two upon nuclear division to match experimental observations. We therefore expect a dilution of cytoskeletal motors during the rapid nuclear division to account for the increase in nuclear order during syncytial embryo development. Experimental measurements of kinesin-5 cluster lifetimes support this theoretical finding.
在合胞胚胎的初始发育过程中，核经历核分裂和空间重排的循环。核出现的空间模式对于随后的细胞化和胚胎形态发生很重要。尽管核包含在共同的细胞质中，但细胞骨架蛋白不均匀地包装在每个核周围的区域中。事实上，微管等细胞骨架元件及其相关的动力蛋白在核之间施加随机力，积极地驱动它们的重排。然而，在每次分裂时核密度增加的情况下，不知道如何平衡随机力以维持核的有序性。在这里，我们研究了从间期 11 开始的几个核分裂过程中黑腹果蝇中的核排列。我们开发了一个理论模型，在该模型中，我们区分了由于核作为弹性基质（即细胞质）中的包含物而产生的长程被动力，以及由肌球蛋白介导的细胞骨架动力学产生的主动、随机力。我们进行了计算机模拟，并量化了观察到的核取向和空间有序度。仅在核分裂时将核密度加倍，模型预测核有序度降低。将结果与跟踪核的实验记录进行比较，我们做出了矛盾的观察结果，发现核分裂后核有序度增加。我们对该比较得出的模型参数的分析表明，总体而言，肌球蛋白蛋白密度以及相对主动力幅度在核分裂时必须降低约两倍才能与实验观察结果相匹配。因此，我们预计在快速核分裂过程中细胞骨架马达的稀释将解释合胞胚胎发育过程中核有序性的增加。对驱动蛋白-5 簇寿命的实验测量支持这一理论发现。
