MRC Centre for Developmental and Biomedical Genetics, and Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK.
Development. 2013 Mar;140(5):1045-54. doi: 10.1242/dev.088724. Epub 2013 Jan 30.
Polarised tissue elongation during morphogenesis involves cells within epithelial sheets or tubes making and breaking intercellular contacts in an oriented manner. Growing evidence suggests that cell adhesion can be modulated by endocytic trafficking of E-cadherin (E-cad), but how this process can be polarised within individual cells is poorly understood. The Frizzled (Fz)-dependent core planar polarity pathway is a major regulator of polarised cell rearrangements in processes such as gastrulation, and has also been implicated in regulation of cell adhesion through trafficking of E-cad; however, it is not known how these functions are integrated. We report a novel role for the core planar polarity pathway in promoting cell intercalation during tracheal tube morphogenesis in Drosophila embryogenesis, and present evidence that this is due to regulation of turnover and levels of junctional E-cad by the guanine exchange factor RhoGEF2. Furthermore, we show that core pathway activity leads to planar-polarised recruitment of RhoGEF2 and E-cad turnover in the epidermis of both the embryonic germband and the pupal wing. We thus reveal a general mechanism by which the core planar polarity pathway can promote polarised cell rearrangements.
形态发生过程中极化的组织延伸涉及上皮片或管内的细胞以定向的方式形成和破坏细胞间的接触。越来越多的证据表明,细胞黏附可以通过 E-钙黏蛋白(E-cad)的内吞作用来调节,但在单个细胞中如何使这个过程极化仍知之甚少。Frizzled(Fz)依赖性核心平面极性途径是胚胎发生中如原肠胚形成等极化细胞重排的主要调节剂,并且也被认为通过 E-cad 的运输调节细胞黏附;然而,这些功能如何整合尚不清楚。我们报道了核心平面极性途径在促进果蝇胚胎发生中气管管形态发生中的细胞插入中的新作用,并提出证据表明,这是由于鸟嘌呤交换因子 RhoGEF2 对连接 E-cad 的周转率和水平的调节。此外,我们还表明,核心途径的活性导致 RhoGEF2 和 E-cad 周转率在胚胎 germband 和蛹翅的表皮中的平面极性募集。因此,我们揭示了核心平面极性途径促进极化细胞重排的一般机制。