Mechanical Forces Program the Orientation of Cell Division during Airway Tube Morphogenesis

Publication date: 5 February 2018
Source:Developmental Cell, Volume 44, Issue 3
Author(s): Zan Tang, Yucheng Hu, Zheng Wang, Kewu Jiang, Cheng Zhan, Wallace F. Marshall, Nan Tang
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.

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Teaser

Tang, Hu et al. demonstrate that a combination of two spindle dynamic behaviors explains the global cell division orientation in the developing airway epithelium. The authors provide insights into how mechanical forces, cell geometry, and oriented cell division function in a highly coordinated manner to ensure normal airway tube morphogenesis.


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