Anllo Lauren, Schüpbach Trudi
Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
Dev Biol. 2016 Jun 15;414(2):193-206. doi: 10.1016/j.ydbio.2016.04.017. Epub 2016 Apr 26.
Cell migration plays crucial roles during development. An excellent model to study coordinated cell movements is provided by the migration of border cell clusters within a developing Drosophila egg chamber. In a mutagenesis screen, we isolated two alleles of the gene rickets (rk) encoding a G-protein-coupled receptor. The rk alleles result in border cell migration defects in a significant fraction of egg chambers. In rk mutants, border cells are properly specified and express the marker Slbo. Yet, analysis of both fixed as well as live samples revealed that some single border cells lag behind the main border cell cluster during migration, or, in other cases, the entire border cell cluster can remain tethered to the anterior epithelium as it migrates. These defects are observed significantly more often in mosaic border cell clusters, than in full mutant clusters. Reduction of the Rk ligand, Bursicon, in the border cell cluster also resulted in migration defects, strongly suggesting that Rk signaling is utilized for communication within the border cell cluster itself. The mutant border cell clusters show defects in localization of the adhesion protein E-cadherin, and apical polarity proteins during migration. E-cadherin mislocalization occurs in mosaic clusters, but not in full mutant clusters, correlating well with the rk border cell migration phenotype. Our work has identified a receptor with a previously unknown role in border cell migration that appears to regulate detachment and polarity of the border cell cluster coordinating processes within the cells of the cluster themselves.
细胞迁移在发育过程中起着至关重要的作用。果蝇发育中的卵室中边缘细胞簇的迁移为研究协调的细胞运动提供了一个绝佳的模型。在一次诱变筛选中,我们分离出了编码一种G蛋白偶联受体的佝偻病基因(rk)的两个等位基因。rk等位基因在相当一部分卵室中导致边缘细胞迁移缺陷。在rk突变体中,边缘细胞被正确指定并表达标记物Slbo。然而,对固定样本和活样本的分析都显示,在迁移过程中,一些单个边缘细胞落后于主要边缘细胞簇,或者在其他情况下,整个边缘细胞簇在迁移时可能会与前上皮细胞相连。这些缺陷在嵌合边缘细胞簇中比在完全突变簇中更常被观察到。边缘细胞簇中Rk配体bursicon的减少也导致了迁移缺陷,这强烈表明Rk信号传导用于边缘细胞簇自身内部的通讯。突变的边缘细胞簇在迁移过程中显示出粘附蛋白E-钙粘蛋白和顶端极性蛋白定位的缺陷。E-钙粘蛋白的错误定位发生在嵌合簇中,而不是在完全突变簇中,这与rk边缘细胞迁移表型密切相关。我们的工作鉴定出了一种在边缘细胞迁移中具有先前未知作用的受体,它似乎调节边缘细胞簇的脱离和极性,协调簇内细胞自身的过程。