Cell shape and intercellular adhesion regulate mitotic spindle orientation

Cell shape and intercellular adhesion regulate mitotic spindle orientation
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细胞形状和细胞间粘附调节有丝分裂纺锤体方向

DOI:
10.1091/mbc.e19-04-0227
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发表时间:
2019-09-01
影响因子:
3.3
通讯作者:
Jiang, Hongyuan
Jiang, Hongyuan
中科院分区:
生物学3区
文献类型:
--
作者:
Li, Jingchen;Cheng, Longcan;Jiang, Hongyuan

文献摘要

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细胞分裂方向在组织形态发生和细胞命运决定中起着至关重要的作用。最近的研究表明,无论是细胞形状还是黏附几何形状都可以调节有丝分裂纺锤体的方向,从而调节细胞分裂的方向。然而,它们如何共同调节纺锤体的方向在很大程度上仍不清楚。在这项工作中,我们使用一个通用的计算模型来研究决定细胞形状和细胞间黏附之间纺锤体取向的竞争机制。我们发现,当晶胞形状各向异性较小时,纺锤形取向主要由胞间黏附所决定,而当晶胞形状各向异性较大时,纺锤形取向主要由晶胞形状所决定。较强的粘附力和适中的粘附力大小可以保证上皮细胞的平面分裂,并具有较大的根尖-基底伸长。我们还发现,当细胞的一侧附着在E-钙粘附素涂层的基质上时,纺锤体的取向可以垂直于粘附区。但细胞压缩后,纺锤形取向由细胞形状决定,当细胞形状各向异性较大时,纺锤形将平行于粘结区。最后,我们证明了细胞形状和三细胞连接之间的竞争也可以有效地调节纺锤体的取向。
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 an 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.