A Tug-of-War between Cell Shape and Polarity Controls Division Orientation to Ensure Robust Patterning in the Mouse Blastocyst

Oriented cell division patterns tissues by modulating cell position and fate. While cell geometry, junctions, cortical tension, and polarity are known to control division orientation, relatively little is known about how these are coordinated to ensure robust patterning. Here, we systematically characterize cell division, volume, and shape changes during mouse pre-implantation development by in toto live imaging. The analysis leads us to a model in which the apical domain competes with cell shape to determine division orientation. Two key predictions of the model are verified experimentally: when outside cells of the 16-cell embryo are released from cell shape asymmetry, the axis of division is guided by the apical domain. Conversely, orientation cues from the apical domain can be overcome by applied shape asymmetry in the 8-cell embryo. We propose that such interplay between cell shape and polarity in controlling division orientation ensures robust patterning of the blastocyst and possibly other tissues. [Display omitted] •Cell division, volume, and shape changes are characterized by in toto embryo imaging•Cell shape and the apical domain compete to determine division orientation•Two key predictions of the model are verified experimentally•The tug-of-war mechanism ensures robust cell allocation and patterning Based on systematic characterization of cell division, volume, and shape changes by in toto imaging, Niwayama et al. propose a model in which a tug-of-war between cell shape and the apical domain determines division orientation to ensure robust cell allocation and patterning in mouse pre-implantation embryos.