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分泌的配体进行发育和形态发生。几种机制调节分泌配体的可用性和分布，确定它们在局部和远距离从其来源发出信号的能力。其中一种机制是 Dally 样蛋白 (Dlp)，一种细胞表面磷脂酰肌醇蛋白聚糖，在果蝇翅盘中表现出双相功能，促进 Wg 源细胞的远距离 Wg 信号传导并抑制源细胞附近的 Wg 信号传导。在卵巢尖端的生殖器中，Dlp 促进 Wg 从帽细胞到卵泡干细胞的远距离分布。然而，germarium 也表达其他Wnts - Wnt2、Wnt4和Wnt6- 在护送细胞中局部起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仍然未知。在这里我们展示了dlp过表达表型是多方面的，并且表型复制了多个Wnt功能丧失表型。dlp过表达表型的每个方面都受到单个Wnt的共表达的抑制，并且每个 Wnt 表现出的抑制模式表明 Wnt 在细菌中具有功能特异性。此外，dlp敲低表型Wnt功能获得性表型。这些数据一起表明 Dlp 抑制了每个 Wnt 的功能。所有四种 Wnt 都与 S2R+ 细胞中的 Dlp 共免疫沉淀，这表明在细菌中，Dlp 隔离 Wnt 以抑制局部旁分泌 Wnt 信号。我们的结果表明，Dlp 调节多个细胞外 Wnt 的可用性，用于在 Germarium 中进行局部旁分泌 Wnt 信号传导。