The Hippo Pathway Regulates Homeostatic Growth of Stem Cell Niche Precursors in the Drosophila Ovary

The Hippo pathway regulates organ size, stem cell proliferation and tumorigenesis in adult organs. Whether the Hippo pathway influences establishment of stem cell niche size to accommodate changes in organ size, however, has received little attention. Here, we ask whether Hippo signaling influences the number of stem cell niches that are established during development of the Drosophila larval ovary, and whether it interacts with the same or different effector signaling pathways in different cell types. We demonstrate that canonical Hippo signaling regulates autonomous proliferation of the soma, while a novel hippo-independent activity of Yorkie regulates autonomous proliferation of the germ line. Moreover, we demonstrate that Hippo signaling mediates non-autonomous proliferation signals between germ cells and somatic cells, and contributes to maintaining the correct proportion of these niche precursors. Finally, we show that the Hippo pathway interacts with different growth pathways in distinct somatic cell types, and interacts with EGFR and JAK/STAT pathways to regulate non-autonomous proliferation of germ cells. We thus provide evidence for novel roles of the Hippo pathway in establishing the precise balance of soma and germ line, the appropriate number of stem cell niches, and ultimately regulating adult female reproductive capacity.Hippo信号通路（Hippo pathway）在成年器官中调控器官大小、干细胞增殖与肿瘤发生过程。然而，Hippo通路是否可通过调控干细胞巢（stem cell niche）的大小以适配器官的尺寸变化，这一问题迄今尚未受到充分关注。本研究旨在探讨：Hippo信号通路是否会影响果蝇幼虫卵巢发育过程中形成的干细胞巢数量，以及其在不同细胞类型中是否与相同或不同的效应信号通路发生相互作用。我们证实，经典Hippo信号通路可调控体细胞的自主性增殖，而一种全新的、不依赖Hippo的约克伊（Yorkie）活性则可调控生殖系的自主性增殖。此外，我们发现Hippo信号通路可介导生殖细胞与体细胞之间的非自主性增殖信号，并有助于维持这类微环境前体细胞的合理比例。最后，我们证明Hippo信号通路在不同的体细胞类型中可与不同的生长通路发生相互作用，并与表皮生长因子受体（EGFR）及JAK/STAT信号通路协同调控生殖细胞的非自主性增殖。综上，本研究为Hippo信号通路在维持体细胞与生殖细胞的精确平衡、调控干细胞巢的适宜数量，以及最终调控成年雌性生殖能力方面的全新作用提供了实验证据。