Neuronal octopamine signaling regulates mating-induced germline stem cell proliferation in femaleDrosophila melanogaster

Abstract

27Stem cells fuel the development and maintenance of tissues. Many studies have addressed how 28 local signals from neighboring niche cells regulate stem cell identity and their proliferative 29 potential. However, the regulation of stem cells by tissue-extrinsic signals in response to external 30 cues remains poorly understood. Here we report that efferent octopaminergic neurons projecting 31 to the ovary are essential for germline stem cell (GSC) proliferation in response to mating in 32 female Drosophila. The neuronal activity of the octopaminergic neurons is required for mating-33 induced GSC proliferation as they relay the mating signal from Sex peptide receptor-positive 34 cholinergic neurons. Octopamine and its receptor Oamb are also required for mating-induced 35 GSC proliferation via intracellular Ca 2+ signaling. Moreover, we identified Matrix 36 metalloproteinase-2 as a downstream component of the octopamine-Ca 2+ signaling to induce 37 GSC proliferation. Our study provides a mechanism describing how neuronal system couples 38 stem cell behavior to external cues through stem cell niche signaling. 39 40 Kim et al., 2016; Nakada et al., 2014). Retinoic acid and thyroid hormone play essential roles in 52 the differentiation of testicular stem cells and neural stem cells, respectively (Gothié et al., 2017; 53 Ikami et al., 2015). In addition, mesenchymal stem cell proliferation is stimulated by adrenaline 54 (Wu et al., 2014). However, the when, how, and why these humoral factors are produced, 55 circulated, and received during stem cell regulation remain to be elucidated. 56The ovaries of the fruit fly Drosophila melanogaster are an excellent model system on 57how stem cell lineages are shaped by both local niche signals and tissue-extrinsic signals 58(Drummond-Barbosa, 2019). D. melanogaster ovary is composed of 16-20 chains of developing 59 egg chambers called ovarioles. The anterior-most region of which, known as the germarium, 60 contains germline stem cells (GSCs) that give rise to the eggs ( Figure 1A and B). GSCs are 61 adjacent to the somatic niche cells, which comprises cap cells, escort cells, and terminal filament 62 cells ( Figure 1A). After GSC divides, one daughter cell that remains attached to the niche cells 63 retains its GSC identity, whereas the remaining daughter cell is displaced away from the niche 64 cells and differentiates into cystoblast (CB). Each CB then undergoes differentiation into 15 65 nurse cells and 1 oocyte in each egg chamber, which is surrounded by somatic follicle cells. 66 GSC niche produces and secretes several local niche signals that regulate the balance 67 between GSC self-renewal and differentiation (Hayashi et al., 2020;Kirilly and Xie, 2007; 68 Spradling et al., 2011). For example, bone morphogenetic protein (BMP) ligands 69 Decapentaplegic (Dpp) and Glass bottom boat (Gbb) are produced from the niche cells and 70 directly activate BMP receptors in GSCs, leading to the repression of the differentiation inducer, 71 bag-of-marbles (bam) (Morrison and Spra...

Drosophila Insulin-Like Peptide 8 (DILP8) in Ovarian Follicle Cells Regulates Ovulation and Metabolism

“…We did not analyze effects of Lgr3 manipulations here, but suggest that this receptor in follicle cells and perhaps in a small set of efferent Lgr3-Gal4 neurons innervating oviduct muscle may be primarily responsible for the ovulation phenotype. It cannot be excluded that other Lgr3-Gal4 expressing neurons in the abdominal ganglia interact with octopaminergic neurons innervating the oviduct and thus indirectly contribute to the known octopamine effects on ovary maturation and ovulation (48,50,51,55,58,59).…”

Drosophilainsulin-like peptide 8 (DILP8) in ovarian follicle cells regulates ovulation and metabolism

“…We did not analyze effects of Lgr3 manipulations here, but suggest that this receptor in follicle cells and perhaps in a small set of efferent Lgr3 neurons innervating oviduct muscle may be primarily responsible for the ovulation phenotype. It cannot be excluded that other Lgr3-expressing neurons in the abdominal ganglia interact with octopaminergic neurons innervating the oviduct and thus indirectly contribute to the known octopamine effects on ovary maturation and ovulation (Lee et al, 2003;Monastirioti, 2003;Lee et al, 2009;Rubinstein and Wolfner, 2013;Deady et al, 2015;Yoshinari et al, 2020).…”