Fox Donald T, Peifer Mark
Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280, USA.
Development. 2007 Feb;134(3):567-78. doi: 10.1242/dev.02748. Epub 2007 Jan 3.
Morphogenesis involves the interplay of different cytoskeletal regulators. Investigating how they interact during a given morphogenetic event will help us understand animal development. Studies of ventral furrow formation, a morphogenetic event during Drosophila gastrulation, have identified a signaling pathway involving the G-protein Concertina (Cta) and the Rho activator RhoGEF2. Although these regulators act to promote stable myosin accumulation and apical cell constriction, loss-of-function phenotypes for each of these pathway members is not equivalent, suggesting the existence of additional ventral furrow regulators. Here, we report the identification of Abelson kinase (Abl) as a novel ventral furrow regulator. We find that Abl acts apically to suppress the accumulation of both Enabled (Ena) and actin in mesodermal cells during ventral furrow formation. Further, RhoGEF2 also regulates ordered actin localization during ventral furrow formation, whereas its activator, Cta, does not. Taken together, our data suggest that there are two crucial preconditions for apical constriction in the ventral furrow: myosin stabilization/activation, regulated by Cta and RhoGEF2; and the organization of apical actin, regulated by Abl and RhoGEF2. These observations identify an important morphogenetic role for Abl and suggest a conserved mechanism for this kinase during apical cell constriction.
形态发生涉及不同细胞骨架调节因子之间的相互作用。研究它们在特定形态发生事件中的相互作用方式将有助于我们理解动物发育过程。对腹沟形成(果蝇原肠胚形成过程中的一种形态发生事件)的研究,已经确定了一条涉及G蛋白Concertina(Cta)和Rho激活剂RhoGEF2的信号通路。尽管这些调节因子的作用是促进肌球蛋白的稳定积累和顶端细胞收缩,但这些信号通路成员各自的功能缺失表型并不相同,这表明还存在其他腹沟调节因子。在此,我们报告鉴定出阿贝尔森激酶(Abl)是一种新的腹沟调节因子。我们发现,在腹沟形成过程中,Abl在顶端发挥作用,抑制中胚层细胞中Enabled(Ena)和肌动蛋白的积累。此外,RhoGEF2在腹沟形成过程中也调节肌动蛋白的有序定位,而其激活剂Cta则不然。综上所述,我们的数据表明,腹沟顶端收缩有两个关键前提条件:由Cta和RhoGEF2调节的肌球蛋白稳定/激活;以及由Abl和RhoGEF2调节的顶端肌动蛋白的组织。这些观察结果确定了Abl在形态发生中的重要作用,并提示了该激酶在顶端细胞收缩过程中的保守机制。