College of Life Sciences, Peking University, Beijing 100871, China; National Institute of Biological Sciences, Beijing 102206, China.
Zhou Pei-yuan Center for Applied Mathematics, Tsinghua University, Beijing 100084, China.
Dev Cell. 2018 Feb 5;44(3):313-325.e5. doi: 10.1016/j.devcel.2017.12.013. Epub 2018 Jan 11.
Oriented cell division plays a key role in controlling organogenesis. The mechanisms for regulating division orientation at the whole-organ level are only starting to become understood. By combining 3D time-lapse imaging, mouse genetics, and mathematical modeling, we find that global orientation of cell division is the result of a combination of two types of spindles with distinct spindle dynamic behaviors in the developing airway epithelium. Fixed spindles follow the classic long-axis rule and establish their division orientation before metaphase. In contrast, rotating spindles do not strictly follow the long-axis rule and determine their division orientation during metaphase. By using both a cell-based mechanical model and stretching-lung-explant experiments, we showed that mechanical force can function as a regulatory signal in maintaining the stable ratio between fixed spindles and rotating spindles. Our findings demonstrate that mechanical forces, cell geometry, and oriented cell division function together in a highly coordinated manner to ensure normal airway tube morphogenesis.
定向细胞分裂在控制器官发生中起着关键作用。调节整个器官水平分裂方向的机制才刚刚开始被理解。通过结合 3D 延时成像、小鼠遗传学和数学建模，我们发现细胞分裂的整体方向是两种具有不同纺锤体动力学行为的纺锤体的组合的结果，这两种纺锤体存在于发育中的气道上皮中。固定纺锤体遵循经典的长轴规则，并在中期之前确定其分裂方向。相比之下，旋转纺锤体并不严格遵循长轴规则，而是在中期确定其分裂方向。通过使用基于细胞的力学模型和拉伸肺外植体实验，我们表明机械力可以作为一种调节信号，维持固定纺锤体和旋转纺锤体之间的稳定比例。我们的研究结果表明，机械力、细胞几何形状和定向细胞分裂以高度协调的方式共同作用，以确保正常的气道管形态发生。
