Department of Cell and Developmental Biology and Program in Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
Department of Cell and Developmental Biology and Program in Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
Dev Biol. 2020 Aug 1;464(1):88-102. doi: 10.1016/j.ydbio.2020.05.004. Epub 2020 May 28.
Cells in multicellular organisms rely on secreted ligands for development and morphogenesis. Several mechanisms modulate the availability and distribution of secreted ligands, determining their ability to signal locally and at long range from their source. One of these mechanisms is Dally-like protein (Dlp), a cell-surface glypican that exhibits biphasic functions in Drosophila wing discs, promoting Wg signaling at long-range from Wg source cells and inhibiting Wg signaling near source cells. In the germarium at the tip of the ovary, Dlp promotes long-range distribution of Wg from cap cells to follicle stem cells. However, the germarium also expresses other Wnts - Wnt2, Wnt4, and Wnt6 - that function locally in escort cells to promote oogenesis. Whether and how local functions of these Wnts are regulated remains unknown. Here we show that the dlp overexpression phenotype is multifaceted and phenocopies multiple Wnt loss-of-function phenotypes. Each aspect of dlp overexpression phenotype is suppressed by co-expression of individual Wnts, and the suppression pattern exhibited by each Wnt suggests that Wnts have functional specificity in the germarium. Further, dlp knockdown phenocopies Wnt gain-of-function phenotypes. Together these data show that Dlp inhibits the functions of each Wnt. All four Wnts co-immunoprecipitate with Dlp in S2R+ cells, suggesting that in the germarium, Dlp sequesters Wnts to inhibit local paracrine Wnt signaling. Our results indicate that Dlp modulates the availability of multiple extracellular Wnts for local paracrine Wnt signaling in the germarium.
多细胞生物中的细胞依赖于分泌的配体来进行发育和形态发生。有几种机制可以调节分泌配体的可用性和分布，从而决定其从源部位进行局部和远程信号传递的能力。其中一种机制是 Dally-like 蛋白（Dlp），它是一种细胞表面糖蛋白聚糖，在果蝇翅膀盘中表现出双相功能，促进 Wg 从 Wg 源细胞进行远程信号传递，并抑制 Wg 在源细胞附近的信号传递。在卵巢顶端的生殖囊中，Dlp 促进 Wg 从帽细胞到滤泡干细胞的远程分布。然而，生殖囊还表达其他 Wnt——Wnt2、Wnt4 和 Wnt6——它们在 escort 细胞中发挥局部作用，以促进卵子发生。这些 Wnt 的局部功能是否以及如何受到调节尚不清楚。在这里，我们表明 dlp 过表达表型是多方面的，并且可以模拟多种 Wnt 功能丧失表型。dlp 过表达表型的每个方面都被单独的 Wnt 共表达所抑制，并且每种 Wnt 表现出的抑制模式表明 Wnt 在生殖囊中具有功能特异性。此外，dlp 敲低可模拟 Wnt 功能获得表型。这些数据表明 Dlp 抑制了每个 Wnt 的功能。在 S2R+细胞中，所有四种 Wnt 都与 Dlp 共免疫沉淀，这表明在生殖囊中，Dlp 将 Wnt 隔离以抑制局部旁分泌 Wnt 信号传递。我们的结果表明，Dlp 调节了生殖囊中多个细胞外 Wnt 用于局部旁分泌 Wnt 信号传递的可用性。
