The Wnt pathway limits BMP signaling outside of the germline stem cell niche in Drosophila ovaries

Abstract

The mechanisms that modulate and limit the signaling output of adult stem cell niches remain poorly understood. To gain further insights into how these microenvironments are regulated in vivo, we performed a candidate gene screen designed to identify factors that restrict BMP signal production to the cap cells that comprise the germline stem cell (GSC) niche of Drosophila ovaries. Through these efforts, we found that disruption of Wnt4 and components of the canonical Wnt pathway results in a complex germ cell phenotype marked by an expansion of GSC-like cells, pre-cystoblasts and cystoblasts in young females. This phenotype correlates with an increase of decapentaplegic (dpp) mRNA levels within escort cells and varying levels of BMP responsiveness in the germline. Further genetic experiments show that Wnt4, which exhibits graded expression in somatic cells of germaria, activates the Wnt pathway in posteriorly positioned escort cells. The activation of the Wnt pathway appears to be limited by the BMP pathway itself, as loss of Mad in escort cells results in the expansion of Wnt pathway activation. Wnt pathway activity changes within germaria during the course of aging, coincident with changes in dpp production. These data suggest that mutual antagonism between the BMP and Wnt pathways in somatic cells helps to regulate germ cell differentiation.

Yorkie and Hedgehog independently restrict BMP production in escort cells to permit germline differentiation in the Drosophila ovary

“…Several constituents of ECs are known to be involved in silencing BMP ligands and facilitators. These include molecules necessary for regulating the cellular processes that contact germline cells (as exemplified by Rho; Kirilly et al, 2011), EGFR (Liu et al, 2010), Wnt pathway components (Hamada-Kawaguchi et al, 2014;Luo et al, 2015;Wang et al, 2015;Mottier-Pavie et al, 2016), Piwi (Ma et al, 2014) and multiple regulators of chromatin modifications (Eliazer et al, 2011;Wang et al, 2011;Xuan et al, 2013;Maimon et al, 2014). Here, we report that the Hh and Hpo/Yki pathways also serve to suppress BMP ligand production in ECs.…”

Coordinating Proliferation, Polarity, and Cell Fate in the Drosophila Female Germline

“…Escort cell protrusions dynamically wrap the dividing cystoblasts and are essential for mitotic division of the cysts, as well as the association of follicle cells with the germline at encapsulation. Like cap cells, escort cells also produce and secrete signaling molecules; Hedgehog, Wnt/Wg, Epidermal Growth Factor (EGF), insulin, and ecdysone signaling all function non-autonomously in escort cells to control germ cell differentiation (Morris and Spradling, 2012;Xuan et al, 2013;Eliazer et al, 2014;König and Shcherbata, 2015;Liu et al, 2015;Lu et al, 2015;Luo et al, 2015;Mottier-Pavie et al, 2016;Huang et al, 2017;Su et al, 2018;Wang and Page-McCaw, 2018;Mao et al, 2019). In general, many of these signals act to sustain the cytoskeletal structure and/or dynamics of escort cell protrusions.…”

Adult Stem Cells and Niche Cells segregate gradually from common precursors that build the adult Drosophila ovary during pupal development

“…The differentiation of germline cysts in the adult germarium depends on interactions with ECs and this has also been seen in some cases during pupal development even though many EC precursors are still dividing during early pupation. Normal Wnt pathway activity is among those shown to be important for this function in ECs and pre-ECs (Hamada-Kawaguchi et al, 2014;Luo et al, 2015;Mottier-Pavie et al, 2016;Upadhyay et al, 2018;Waghmare and Page-McCaw, 2018;Wang et al, 2015;Wang and Page-McCaw, 2018). It is not known what drives ordered posterior movement of germline cysts in adult germaria but this also may depend on EC interactions (Banisch et al, 2017).…”