Tight junctions in mammals and septate junctions in insects are essential for epithelial integrity. We show here that, in the Drosophila intestine, smooth septate junction proteins provide barrier and signaling functions. During an RNAi screen for genes that regulate adult midgut tissue growth, we found that loss of two smooth septate junction components, Snakeskin and Mesh, caused a hyperproliferation phenotype. By examining epitope-tagged endogenous Snakeskin and Mesh, we demonstrate that the two proteins are present in the cytoplasm of differentiating enteroblasts and in cytoplasm and septate junctions of mature enterocytes. In both enteroblasts and enterocytes, loss of Snakeskin and Mesh causes Yorkie-dependent expression of the JAK-STAT pathway ligand Upd3, which in turn promotes proliferation of intestinal stem cells. Snakeskin and Mesh form a complex with each other, with other septate junction proteins and with Yorkie. Therefore, the Snakeskin-Mesh complex has both barrier and signaling function to maintain stem cell-mediated tissue homeostasis.

哺乳动物的紧密连接和昆虫的分隔连接对于上皮的完整性至关重要。我们在这里表明，在果蝇中在肠中，平滑的分隔连接蛋白可提供屏障和信号传导功能。在RNAi筛选中，调节成年中肠组织生长的基因期间，我们发现两个光滑的先天性连接成分Snakeskin和Mesh的缺失导致过度增殖表型。通过检查表位标记的内源性Snakeskin和Mesh，我们证明了这两种蛋白质存在于分化成肠细胞的细胞质中以及成熟肠细胞的细胞质和分隔连接中。在成肠细胞和肠上皮细胞中，蛇皮和网状细胞的缺失会导致JAK-STAT途径配体Upd3的约克依赖表达，进而促进肠干细胞的增殖。Snakeskin和Mesh彼此，其他分隔连接蛋白以及Yorkie形成复合物。因此，