Apoptosis and Proliferation Control Laboratory, Cancer Research UK, London Research Institute, London, UK.
EMBO J. 2013 Oct 30;32(21):2790-803. doi: 10.1038/emboj.2013.197. Epub 2013 Sep 10.
Orientation of cell divisions is a key mechanism of tissue morphogenesis. In the growing Drosophila wing imaginal disc epithelium, most of the cell divisions in the central wing pouch are oriented along the proximal-distal (P-D) axis by the Dachsous-Fat-Dachs planar polarity pathway. However, cells at the periphery of the wing pouch instead tend to orient their divisions perpendicular to the P-D axis despite strong Dachs polarization. Here, we show that these circumferential divisions are oriented by circumferential mechanical forces that influence cell shapes and thus orient the mitotic spindle. We propose that this circumferential pattern of force is not generated locally by polarized constriction of individual epithelial cells. Instead, these forces emerge as a global tension pattern that appears to originate from differential rates of cell proliferation within the wing pouch. Accordingly, we show that localized overgrowth is sufficient to induce neighbouring cell stretching and reorientation of cell division. Our results suggest that patterned rates of cell proliferation can influence tissue mechanics and thus determine the orientation of cell divisions and tissue shape.
细胞分裂方向是组织形态发生的关键机制。在生长中的果蝇翅 imaginal 盘上皮组织中，大多数位于中央翅囊中细胞的分裂方向沿近端-远端（P-D）轴由 Dachsous-Fat-Dachs 平面极性途径决定。然而，尽管 Dachs 极化很强，翅囊中边缘的细胞倾向于将它们的分裂垂直于 P-D 轴。在这里，我们表明这些周向分裂是由影响细胞形状并因此决定有丝分裂纺锤体方向的周向机械力决定的。我们提出，这种周向力模式不是由单个上皮细胞的极化收缩在局部产生的。相反，这些力表现为一种整体张力模式，似乎源自翅囊中细胞增殖率的差异。因此，我们表明局部过度生长足以诱导相邻细胞拉伸和细胞分裂方向的重新定向。我们的结果表明，有模式的细胞增殖率可以影响组织力学，从而决定细胞分裂的方向和组织形状。
