Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Dev Biol. 2009 Dec 1;336(1):68-75. doi: 10.1016/j.ydbio.2009.09.033. Epub 2009 Sep 25.
Lethal giant larvae (Lgl) plays a critical role in establishment of cell polarity in epithelial cells. While Frizzled/Dsh signaling has been implicated in the regulation of the localization and activity of Lgl, it remains unclear whether specific Wnt ligands are involved. Here we show that Wnt5a triggers the release of Lgl from the cell cortex into the cytoplasm with the concomitant decrease in Lgl stability. The observed changes in Lgl localization were independent of atypical PKC (aPKC), which is known to influence Lgl distribution. In ectodermal cells, both Wnt5a and Lgl triggered morphological and molecular changes characteristic of apical constriction, whereas depletion of their functions prevented endogenous and ectopic bottle cell formation. Furthermore, Lgl RNA partially rescued bottle cell formation in embryos injected with a dominant negative Wnt5a construct. These results suggest a molecular link between Wnt5a and Lgl that is essential for apical constriction during vertebrate gastrulation.
致死性巨幼虫 (Lgl) 在上皮细胞的细胞极性建立中发挥着关键作用。虽然 Frizzled/Dsh 信号在 Lgl 的定位和活性调节中起作用,但尚不清楚是否涉及特定的 Wnt 配体。在这里,我们表明 Wnt5a 将 Lgl 从细胞膜释放到细胞质中,同时降低 Lgl 的稳定性。观察到的 Lgl 定位变化与非典型 PKC(aPKC)无关,aPKC 已知会影响 Lgl 的分布。在外胚层细胞中,Wnt5a 和 Lgl 都触发了具有顶端缢缩特征的形态和分子变化,而它们的功能缺失则阻止了内源性和异位瓶状细胞的形成。此外,在注射显性负性 Wnt5a 构建体的胚胎中,Lgl RNA 部分挽救了瓶状细胞的形成。这些结果表明 Wnt5a 和 Lgl 之间存在分子联系,这对于脊椎动物原肠胚形成期间的顶端缢缩是必不可少的。