Bergstralh Dan T, Lovegrove Holly E, St Johnston Daniel
The Gurdon Institute and the Department of Genetics, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Nat Cell Biol. 2015 Nov;17(11):1497-1503. doi: 10.1038/ncb3248. Epub 2015 Sep 28.
Cells in simple epithelia orient their mitotic spindles in the plane of the epithelium so that both daughter cells are born within the epithelial sheet. This is assumed to be important to maintain epithelial integrity and prevent hyperplasia, because misaligned divisions give rise to cells outside the epithelium. Here we test this assumption in three types of Drosophila epithelium; the cuboidal follicle epithelium, the columnar early embryonic ectoderm, and the pseudostratified neuroepithelium. Ectopic expression of Inscuteable in these tissues reorients mitotic spindles, resulting in one daughter cell being born outside the epithelial layer. Live imaging reveals that these misplaced cells reintegrate into the tissue. Reducing the levels of the lateral homophilic adhesion molecules Neuroglian or Fasciclin 2 disrupts reintegration, giving rise to extra-epithelial cells, whereas disruption of adherens junctions has no effect. Thus, the reinsertion of misplaced cells seems to be driven by lateral adhesion, which pulls cells born outside the epithelial layer back into it. Our findings reveal a robust mechanism that protects epithelia against the consequences of misoriented divisions.
简单上皮组织中的细胞将其有丝分裂纺锤体定向于上皮平面内，以便两个子细胞都在上皮层内产生。这被认为对维持上皮完整性和防止增生很重要，因为纺锤体排列错误会产生上皮层外的细胞。在这里，我们在三种果蝇上皮组织中测试了这一假设；立方体细胞的卵泡上皮、柱状早期胚胎外胚层和假复层神经上皮。在这些组织中异位表达无柄蛋白会使有丝分裂纺锤体重新定向，导致一个子细胞在上皮层外产生。实时成像显示，这些位置错误的细胞会重新整合到组织中。降低侧向同型黏附分子神经胶质蛋白或 Fasciclin 2 的水平会破坏重新整合，产生上皮外细胞，而黏着连接的破坏则没有影响。因此，位置错误细胞的重新插入似乎是由侧向黏附驱动的，侧向黏附将在上皮层外产生的细胞拉回到上皮层中。我们的研究结果揭示了一种强大的机制，可保护上皮组织免受纺锤体定向错误分裂的影响。
