Mechanical Forces Program the Orientation of Cell Division during Airway Tube Morphogenesis
Zan Tanga b, Yucheng Huc, Zheng Wangb d, Kewu Jiangb e, Cheng Zhanb, Wallace F. Marshallf g✉, Nan Tangb h✉
- aCollege of Life Sciences, Peking University, Beijing 100871, China
- bNational Institute of Biological Sciences, Beijing 102206, China
- cZhou Pei-yuan Center for Applied Mathematics, Tsinghua University, Beijing 100084, China
- dGraduate School of Peking Union Medical College, Beijing 100730, China
- eCollege of Life Sciences, Beijing Normal University, Beijing 100875, China
- fDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: wallace.marshall@ucsf.edu
- gDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA
- hNational Institute of Biological Sciences, Beijing 102206, China. Electronic address: tangnan@nibs.ac.cn
- ✉Corresponding author
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Abstract
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.
TL;DRThe findings demonstrate that mechanical forces, cell geometry, and oriented cell division function together in a highly coordinated manner to ensure normal airway tube morphogenesis. (Semantic Scholar)