Interfakultäres Institut für Zellbiologie, Abteilung Genetik der Tiere, Fachbereich für Biologie, Universität Tübingen, Auf der Morgenstelle 28, D-72076 Tübingen, Germany.
J Cell Sci. 2012 Aug 15;125(Pt 16):3801-12. doi: 10.1242/jcs.101196. Epub 2012 May 2.
The PDZ-GEF protein Dizzy (Dzy) and its downstream GTPase Rap1 have pleiotropic roles during development of the Drosophila embryo. Here, we show that maternally provided Dzy and Rap1 first function during ventral furrow formation (VFF) where they are critical to guarantee rapid apical cell constrictions. Contraction of the apical actomyosin filament system occurs independently of Dzy and Rap1, but loss of Dzy results in a delayed establishment of the apical adherens junction (AJ) belt, whereas in the absence of Rap1 only a fragmentary apical AJ belt is formed in the epithelium. The timely establishment of apical AJs appears to be essential for coupling actomyosin contractions to cell shape change and to assure completion of the ventral furrow. Immediately after VFF, the downregulation of Dzy and Rap1 is necessary to allow normal mesodermal development to continue after the epithelial-to-mesenchymal transition, as overexpression of Dzy or of constitutively active Rap1 compromises mesodermal migration and monolayer formation. We propose that Dzy and Rap1 are crucial factors regulating the dynamics of AJs during gastrulation.
PDZ-GEF 蛋白 Dizzy(Dzy)及其下游 GTPase Rap1 在果蝇胚胎发育过程中具有多种作用。在这里,我们表明,母体提供的 Dzy 和 Rap1 首先在腹沟形成(VFF)期间发挥作用,它们对于保证快速的顶端细胞收缩至关重要。顶端肌动球蛋白丝系统的收缩独立于 Dzy 和 Rap1 发生,但 Dzy 的缺失导致顶端黏着连接(AJ)带的建立延迟,而 Rap1 的缺失仅导致上皮中形成不完整的顶端 AJ 带。顶端 AJ 的及时建立似乎对于将肌动球蛋白收缩与细胞形状变化偶联以及确保腹沟完成至关重要。VFF 之后,Dzy 和 Rap1 的下调对于允许上皮到间质过渡后正常中胚层发育继续是必要的,因为 Dzy 的过表达或组成性激活的 Rap1 会损害中胚层迁移和单层形成。我们提出,Dzy 和 Rap1 是调节原肠胚形成期间 AJ 动态的关键因素。