Vanderploeg Jessica, Jacobs J Roger
Department of Biology, McMaster University, 1280 Main Street West, Hamilton, ON, Canada L8S 4K1.
Department of Biology, McMaster University, 1280 Main Street West, Hamilton, ON, Canada L8S 4K1.
Dev Biol. 2015 Sep 15;405(2):189-201. doi: 10.1016/j.ydbio.2015.04.024. Epub 2015 May 7.
Fluid- and gas-transporting tubular organs are critical to metazoan development and homeostasis. Tubulogenesis involves cell polarization and morphogenesis to specify the luminal, adhesive, and basal cell domains and to establish an open lumen. We explore a requirement for Talin, a cytoplasmic integrin adapter, during Drosophila melanogaster embryonic heart tube development. Talin marks the presumptive luminal domain and is required to orient and develop an open luminal space within the heart. Genetic analysis demonstrates that loss of zygotic or maternal-and-zygotic Talin disrupts heart cell migratory dynamics, morphogenesis, and polarity. Talin is essential for subsequent polarization of luminal determinants Slit, Robo, and Dystroglycan as well as stabilization of extracellular and intracellular integrin adhesion factors. In the absence of Talin function, mini-lumens enriched in luminal factors form in ectopic locations. Rescue experiments performed with mutant Talin transgenes suggest that actin-binding is required for normal lumen formation, but not for initial heart cell polarization. We propose that Talin provides instructive cues to position the luminal domain and coordinate the actin cytoskeleton during Drosophila heart lumen development.
流体和气体运输的管状器官对于后生动物的发育和体内平衡至关重要。管状发生涉及细胞极化和形态发生，以确定管腔、黏附性和基底细胞结构域，并建立开放的管腔。我们探究了一种细胞质整合素衔接蛋白踝蛋白（Talin）在黑腹果蝇胚胎心脏管发育过程中的作用。踝蛋白标记了假定的管腔结构域，并且对于在心脏内定向和发育开放的管腔空间是必需的。遗传分析表明，合子型或母源-合子型踝蛋白的缺失会破坏心脏细胞的迁移动力学、形态发生和极性。踝蛋白对于管腔决定因子Slit、Robo和肌营养不良聚糖（Dystroglycan）随后的极化以及细胞外和细胞内整合素黏附因子的稳定至关重要。在缺乏踝蛋白功能的情况下，富含管腔因子的微管腔在异位位置形成。用突变型踝蛋白转基因进行的拯救实验表明，肌动蛋白结合对于正常管腔形成是必需的，但对于初始心脏细胞极化则不是必需的。我们提出，踝蛋白在果蝇心脏管腔发育过程中为定位管腔结构域和协调肌动蛋白细胞骨架提供了指导性线索。
