Department of Molecular Biology, Howard Hughes Medical Institute, Princeton University, Princeton, NJ 08544, USA.
Dev Cell. 2013 May 13;25(3):299-309. doi: 10.1016/j.devcel.2013.04.002. Epub 2013 Apr 25.
Localized cell shape change initiates epithelial folding, while neighboring cell invagination determines the final depth of an epithelial fold. The mechanism that controls the extent of invagination remains unknown. During Drosophila gastrulation, a higher number of cells undergo invagination to form the deep posterior dorsal fold, whereas far fewer cells become incorporated into the initially very similar anterior dorsal fold. We find that a decrease in α-catenin activity causes the anterior fold to invaginate as extensively as the posterior fold. In contrast, constitutive activation of the small GTPase Rap1 restricts invagination of both dorsal folds in an α-catenin-dependent manner. Rap1 activity appears spatially modulated by Rapgap1, whose expression levels are high in the cells that flank the posterior fold but low in the anterior fold. We propose a model whereby distinct activity states of Rap1 modulate α-catenin-dependent coupling between junctions and actin to control the extent of epithelial invagination.
局部细胞形状变化启动上皮折叠，而相邻细胞内陷决定上皮折叠的最终深度。控制内陷程度的机制尚不清楚。在果蝇胚胎发生过程中，更多的细胞发生内陷形成深后背褶皱，而最初非常相似的前背褶皱只有很少的细胞参与。我们发现，α-连环蛋白活性的降低会导致前背褶皱像后背褶皱一样广泛内陷。相比之下，小 GTPase Rap1 的组成性激活以 α-连环蛋白依赖性的方式限制了两个背褶皱的内陷。Rap1 活性似乎受到 Rapgap1 的空间调节，其表达水平在后背褶皱的侧翼细胞中较高，而在前背褶皱中较低。我们提出了一个模型，即 Rap1 的不同活性状态调节α-连环蛋白依赖性连接子和肌动蛋白之间的偶联，以控制上皮内陷的程度。
