Abstract

SummaryOriented 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.

Highlights

  • Tissue patterning is driven by position-dependent differentiation, coordinated movement, and division of cells

  • The live-imaging analysis showed that in contrast to the preceding stage, most cells undergo symmetric divisions during the 16–32 cell transition (Figures 1A and 1B; Video S1), in agreement with an earlier study (Watanabe et al, 2014). Since this occurs despite the persistence of the apical domain, we investigated the mechanism underlying this abrupt change in cell division pattern

  • To understand the mechanism of the rapid increase in the inside cells after the release of compression, we examined the first divisions in control and (B) The introduction of cell shape asymmetry in the 8-cell blastomeres changes their division orientation

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Summary

Introduction

Tissue patterning is driven by position-dependent differentiation, coordinated movement, and division of cells. The first cell lineage segregation results in the formation of the blastocyst in which an inner cell mass (ICM) is surrounded by outer trophectoderm (TE) cells (Rossant and Tam, 2009; Yamanaka et al, 2006) This position-dependent cell fate specification has been studied for decades (Tarkowski and Wroblewska, 1967). When 8-cell embryos were compressed to a height of 20 mm, the aspect ratio of individual cells reached 3.0 on average (N = 15 embryos, Figure 4C; Video S5). Under this condition, these cells underwent symmetric divisions, as judged from symmetric segregation of the apical domain

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