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Cell division orientation plays an essential role in tissue morphogenesis and cell fate decision. Recent studies showed that either cell shape or adhesion geometry can regulate the orientation of mitotic spindles, and thereby the cell division orientation. However, how they together regulate the spindle orientation remains largely unclear. In this work, we use a general computational model to investigate the competitive mechanism of determining the spindle orientation between cell shape and intercellular adhesion in epithelial cells. We find the spindle orientation is dominated by the intercellular adhesion when the cell shape anisotropy is small, but dominated by the cell shape when the shape anisotropy is large. A strong adhesion and moderate adhesive size can ensure the planar division of epithelial cells with large apico-basal elongation. We also find the spindle orientation could be perpendicular to the adhesive region when only one side of the cell is adhered to E-cadherin-coated matrix. But after the cell is compressed, the spindle orientation is governed by the cell shape and the spindle will be parallel to the adhesive region when the cell shape anisotropy is large. Finally, we demonstrate the competition between cell shape and tricellular junctions can also effectively regulate the spindle orientation. Movie S1 Movie S1 Positioning and orientation of simulated spindles in round cells without adhesion. Several examples show that the spindles in round cells without adhesion can always be positioned to the cell center from random initial conditions in the simulations, but the spindle orientation is randomly distributed since the cell shape and the cortical parameters are isotropic. The cell diameter is 20 µm. Movie S2 Movie S2 Positioning and orientation of simulated spindles in stretched-shaped cells without adhesion. In the cells with the stadium shape (left) or the elliptical shape (right), the spindles can always be positioned to the cell center and oriented along the long axis of the cell shape from random initial conditions in the simulations. The aspect ratio of the shape are all 1.5, and the area is the same as the 20 µm-diameter round cell. Two examples are provided for each shape. Movie S3 Movie S3 Orientation of simulated spindles in the cells with bilateral symmetric adhesion and various aspect ratios of the stadium shape. The stadium-shaped cells have the bilateral symmetric adhesion (red marked) whose parameters are k=11 and L=12 µm, and the aspect ratio is given as λ=1, 1.2, 1.4, or 2. In these cases, the stable spindle orientation transits from the horizontal to the orthogonal direction with the increase of the cell aspect ratio as the cell area is constant. Movie S4 Movie S4 Orientation of simulated spindles in the cells with unilateral adhesion and various aspect ratios of the stadium shape. The stadium-shaped cells have the unilateral adhesion (red marked) whose parameters are k=11 and that L increases with the aspect ratio, and the aspect ratio is given as λ=1, 1.2, 1.5, or 2. In these cases, the stable spindle orientation transits from the perpendicular to the parallel direction to the adhesion region with the increase of the cell aspect ratio. Movie S5 Movie S5 Orientation of simulated spindles in typical polygonal cells with and without the mechanism of tricellular junctions. Two typical cell shapes are selected, in which the tricellular junction polarity (red dotted) and the cell shape polarity are consistent and inconsistent, respectively. The simulated spindle can orient along the cell shape polarity without the tricellular junction mechanism, but along the tricellular junction polarity with the tricellular junction mechanism. Movie S6 Movie S6 Orientation of simulated spindles in the cells with tricellular junctions and various aspect ratios of the stadium shape. The stadium-shaped cells have the tricellular junctions (red dotted), and the aspect ratio is given as λ=1.2 or 1.8. In these cases, the stable spindle orientation transits from the tricellular junction polarity to the cell shape polarity with the increase of the cell aspect ratio as the cell area is constant.
This article was published in the following journal.
Name: Molecular biology of the cell
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