Institute of Genetics, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary.
PLoS One. 2011;6(7):e22229. doi: 10.1371/journal.pone.0022229. Epub 2011 Jul 20.
Morphogenesis, the establishment of the animal body, requires the coordinated rearrangement of cells and tissues regulated by a very strictly-determined genetic program. Dorsal closure of the epithelium in the Drosophila melanogaster embryo is one of the best models for such a complex morphogenetic event. To explore the genetic regulation of dorsal closure, we carried out a large-scale RNA interference-based screen in combination with in vivo time-lapse microscopy and identified several genes essential for the closure or affecting its dynamics. One of the novel dorsal closure genes, the small GTPase activator pebble (pbl), was selected for detailed analysis. We show that pbl regulates actin accumulation and protrusion dynamics in the leading edge of the migrating epithelial cells. In addition, pbl affects dorsal closure dynamics by regulating head involution, a morphogenetic process mechanically coupled with dorsal closure. Finally, we provide evidence that pbl is involved in closure of the adult thorax, suggesting its general requirement in epithelial closure processes.
形态发生，即动物体的建立，需要细胞和组织的协调重排，而这些重排受一个非常严格的遗传程序调控。果蝇胚胎的外胚层背侧闭合是这种复杂形态发生事件的最佳模型之一。为了探索背侧闭合的遗传调控，我们进行了大规模的基于 RNA 干扰的筛选，结合体内实时显微镜观察，鉴定了几个对闭合或影响其动力学过程至关重要的基因。其中一个新的背侧闭合基因，小分子 GTP 酶激活蛋白 pebble(pbl)，被选为详细分析的对象。我们发现 pbl 调节迁移上皮细胞前缘的肌动蛋白积累和突起动力学。此外，pbl 通过调节头部内卷，一个与背侧闭合机械偶联的形态发生过程，影响背侧闭合动力学。最后，我们提供了证据表明 pbl 参与了成虫胸部的闭合，这表明它在上皮闭合过程中具有普遍的需求。
