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Dr. Nan Tang’s laboratory identified a new mechanism in regulating orientation of cell division during airway tube mophogenesis.

Publication Date:2018/01/12

On January 11, 2018, Dr. Nan Tang’s laboratory published a paper entitled “Mechanical forces program the orientation of cell division during airway tube morphogenesis” in the Developmental cell. In this study, they demonstrate that mechanical forces, cell geometry, and oriented cell division function together in a highly coordinated manner to ensure normal airway tube morphogenesis.

Oriented cell division plays a key role in controlling organogenesis. However, the mechanisms for regulating cell division orientation at the tissue or whole-organ level are only starting to become understood. Using mouse genetics,quantitative cell biology with 3D time-lapse imaging, and mathematical modeling, researchers found two types of spindles with distinct spindle dynamic behaviors in the developing airway epithelium:one type of spindlesfixes their orientation within the first 6 minutes during metaphase (fixed-spindles);the other type of spindles does not come to a complete stop during metaphase (rotating-spindles).Most of fixed-spindles divide along the tube longitudinal axis, while the dividing angles of rotating-spindles were randomly distributed. The spatial and temporal relationship between fixed-spindles and rotating-spindles revealed that there is no significant local correlation between the position fixed-spindles and rotating-spindles, while the occurrence of a fixed-spindle and the occurrence of a rotating-spindle over time are not independent of each other.

The cell shape plays animportant role in controlling the orientation of cell divisions.There is an empirically rules named “long-axis rule”, which a mitotic cell tends to divide along its long axis. By measuring the aspect ratio of fixed-spindle cells and rotating-spindle cells before metaphase, researchersfound the fixed-spindle cells are more elongated than rotating-spindlecells. The division orientation of fixed-spindle cells is highly correlated with their interphase long-axis, while the division orientation in rotating-spindle cells is not correlated with their interphase long-axis. Considering that airway tube development is a dynamic process involving highly complex cellular and genetic interactions in space and time, researchersused a ‘cell-based mechanical model’ to determine mechanical force can function as a regulatory signal in maintaining the ratio between fixed-spindles and rotating-spindles. By stretching lung explants, researchersdemonstratedthat mechanical forces play an important role in controlling mitotic spindle angle distribution in the developing airway epithelium.

Zan Tanga PhD student of the PTN programfrom Dr. Nan Tang’s lab and Yucheng Hu from Zhou Pei-yuan Center for Applied Mathematics in Tsinghua University are the co-first authors of this article.Other contributors include Zheng Wang and Kewu Jiang from Dr. Nan Tang’s lab, Dr. Cheng Zhan from NIBS imaging facility. Dr. Nan Tang and Dr. Wallace F. Marshall from UCSF are the corresponding authors.This research was supported bythe National Basic Research Program of China 973 Programs, National Science Foundation of China grant, and carried out at National Institute of Biological Sciences, Beijing.