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During embryonic lung development, epithelial tubes branch to form a complex conducting airway network.The sizes and shapes of lung epithelial tubes are critical for lung function.Our previous study demonstrated that the distribution of mitotic spindle angles in airway epithelium controls airway tube shape.By employing approaches including mouse genetics, three-dimensional time-lapse imaging with mathematical modeling, we investigated the cellular mechanisms by which the spindle orientation is controlled.We found that there are two different spindle rotation behaviors in airway epithelial cells.Our data demonstrated that the spindle rotation behavior determines the mitotic spindle orientation.We therefore propose a novel mechanism for regulating spindle orientation during airway tube morphogenesis.