JAK-STAT-dependent contact between follicle cells and the oocyte controls Drosophila anterior-posterior polarity and germline development.

The number of embryonic primordial germ cells in Drosophila is determined by the quantity of germ plasm, whose assembly starts in the posterior region of the oocyte during oogenesis. Here, we report that extending JAK-STAT activity in the posterior somatic follicular epithelium leads to an excess of primordial germ cells in the future embryo. We show that JAK-STAT signaling is necessary for the differentiation of approximately 20 specialized follicle cells maintaining tight contact with the oocyte. These cells define, in the underlying posterior oocyte cortex, the anchoring of the germ cell determinant oskar mRNA. We reveal that the apical surface of these posterior anchoring cells extends long filopodia penetrating the oocyte. We identify two JAK-STAT targets in these cells that are each sufficient to extend the zone of contact with the oocyte, thereby leading to production of extra primordial germ cells. JAK-STAT signaling thus determines a fixed number of posterior anchoring cells required for anterior-posterior oocyte polarity and for the development of the future germline.

E-cadherin acts as a positive regulator of the JAK-STAT signaling pathway during Drosophila oogenesis.

The JAK-STAT pathway is evolutionary conserved. The simplicity of this signaling in Drosophila, due to the limited redundancy between pathway components, makes it an ideal model for investigation. In the Drosophila follicular epithelium, highly stereotyped functions of JAK-STAT signaling have been well characterized, but how signaling activity is regulated precisely to allow the different outcomes is not well understood. In this tissue, the ligand is secreted by the polar cells positioned at each follicle extremity, thus generating a gradient of JAK-STAT activity in adjacent cells. One way to control the delivered quantity of ligand is by regulating the number of polar cells, which is reduced by apoptosis to exactly two at each pole by mid-oogenesis. Hence, JAK-STAT activity is described as symmetrical between follicle anterior and posterior regions. Here, we show that JAK-STAT signaling activity is actually highly dynamic, resulting in asymmetry between poles by mid-oogenesis. Interestingly, we found similar temporal dynamics at follicle poles in the accumulation of the adherens junction E-cadherin protein. Remarkably, E-cadherin and JAK-STAT signaling not only display patterning overlaps but also share functions during oogenesis. In particular, we show that E-cadherin, like JAK-STAT signaling, regulates polar cell apoptosis non-cell-autonomously from follicle cells. Finally, our work reveals that E-cadherin is required for optimal JAK-STAT activity throughout oogenesis and that E-cadherin and Stat92E, the transcription factor of the pathway, form part of a physical complex in follicle cells. Taken together, our study establishes E-cadherin as a new positive regulator of JAK-STAT signaling during oogenesis.

The Bric-à-Brac BTB/POZ transcription factors are necessary in niche cells for germline stem cells establishment and homeostasis through control of BMP/DPP signaling in the Drosophila melanogaster ovary.

Many studies have focused on the mechanisms of stem cell maintenance via their interaction with a particular niche or microenvironment in adult tissues, but how formation of a functional niche is initiated, including how stem cells within a niche are established, is less well understood. Adult Drosophila melanogaster ovary Germline Stem Cell (GSC) niches are comprised of somatic cells forming a stack called a Terminal Filament (TF) and associated Cap and Escort Cells (CCs and ECs, respectively), which are in direct contact with GSCs. In the adult ovary, the transcription factor Engrailed is specifically expressed in niche cells where it directly controls expression of the decapentaplegic (dpp) gene encoding a member of the Bone Morphogenetic Protein (BMP) family of secreted signaling molecules, which are key factors for GSC maintenance. In larval ovaries, in response to BMP signaling from newly formed niches, adjacent primordial germ cells become GSCs. The bric-à-brac paralogs (bab1 and bab2) encode BTB/POZ domain-containing transcription factors that are expressed in developing niches of larval ovaries. We show here that their functions are necessary specifically within precursor cells for TF formation during these stages. We also identify a new function for Bab1 and Bab2 within developing niches for GSC establishment in the larval ovary and for robust GSC maintenance in the adult. Moreover, we show that the presence of Bab proteins in niche cells is necessary for activation of transgenes reporting dpp expression as of larval stages in otherwise correctly specified Cap Cells, independently of Engrailed and its paralog Invected (En/Inv). Moreover, strong reduction of engrailed/invected expression during larval stages does not impair TF formation and only partially reduces GSC numbers. In the adult ovary, Bab proteins are also required for dpp reporter expression in CCs. Finally, when bab2 was overexpressed at this stage in somatic cells outside of the niche, there were no detectable levels of ectopic En/Inv, but ectopic expression of a dpp transgene was found in these cells and BMP signaling activation was induced in adjacent germ cells, which produced GSC-like tumors. Together, these results indicate that Bab transcription factors are positive regulators of BMP signaling in niche cells for establishment and homeostasis of GSCs in the Drosophila ovary.