Proliferating animal cells are able to orient their mitotic spindles along their interphase cell axis, setting up the axis of cell division, despite rounding up as they enter mitosis. This has previously been attributed to molecular memory and, more specifically, to the maintenance of adhesions and retraction fibers in mitosis [1, 2, 3, 4, 5, 6], which are thought to act as local cues that pattern cortical Gαi, LGN, and nuclear mitotic apparatus protein (NuMA) [3, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18]. This cortical machinery then recruits and activates Dynein motors, which pull on astral microtubules to position the mitotic spindle. Here, we reveal a dynamic two-way crosstalk between the spindle and cortical motor complexes that depends on a Ran-guanosine triphosphate (GTP) signal [12], which is sufficient to drive continuous monopolar spindle motion independently of adhesive cues in flattened human cells in culture. Building on previous work [1, 12, 19, 20, 21, 22, 23], we implemented a physical model of the system that recapitulates the observed spindle-cortex interactions. Strikingly, when this model was used to study spindle dynamics in cells entering mitosis, the chromatin-based signal was found to preferentially clear force generators from the short cell axis, so that cortical motors pulling on astral microtubules align bipolar spindles with the interphase long cell axis, without requiring a fixed cue or a physical memory of interphase shape. Thus, our analysis shows that the ability of chromatin to pattern the cortex during the process of mitotic rounding is sufficient to translate interphase shape into a cortical pattern that can be read by the spindle, which then guides the axis of cell division.

增殖的动物细胞能够沿着间期细胞轴定向有丝分裂纺锤体，建立细胞分裂轴，尽管在进入有丝分裂时会四舍五入。之前这被归因于分子记忆，更具体地说，归因于有丝分裂中粘连和回缩纤维的维持[1,2,3,4,5,6]，它们被认为是形成皮质 Gαi 模式的局部线索， LGN 和核有丝分裂装置蛋白 (NuMA) [3,7,8,9,10,11,12,13,14,15,16,17,18]。然后，这种皮质机制招募并激活动力蛋白马达，该马达拉动星体微管来定位有丝分裂纺锤体。在这里，我们揭示了纺锤体和皮质运动复合体之间的动态双向串扰，该串扰取决于三磷酸鸟苷（GTP）信号[12]，该信号足以驱动连续的单极纺锤体运动，独立于扁平人类细胞中的粘附信号在文化中。基于之前的工作 [1,12,19,20,21,22,23]，我们实现了系统的物理模型，概括了观察到的纺锤体-皮层相互作用。引人注目的是，当该模型用于研究进入有丝分裂的细胞中的纺锤体动力学时，发现基于染色质的信号优先清除短细胞轴上的力发生器，以便拉动星体微管的皮质马达将双极纺锤体与间期长细胞对齐轴，不需要固定提示或相间形状的物理记忆。因此，我们的分析表明，染色质在有丝分裂变圆过程中形成皮质图案的能力足以将间期形状转化为纺锤体可以读取的皮质图案，然后纺锤体引导细胞分裂轴。