Female-germline specific protein Sakura interacts with Otu and is crucial for germline stem cell renewal and differentiation and oogenesis

During oogenesis, self-renewal and differentiation of germline stem cells (GSCs) must be tightly regulated. TheDrosophilafemale germline serves as an excellent model for studying these regulatory mechanisms. Here, we report that a previously uncharacterized geneCG14545, which we namedsakura, is essential for oogenesis and female fertility inDrosophila. Sakura is predominantly expressed in the ovaries, particularly in the germline cells, including GSCs.sakuranull mutant female flies display rudimentary ovaries with germline-less and tumorous phenotypes, fail to produce eggs, and are completely sterile. The germline-specific depletion ofsakuraimpairs Dpp/BMP signaling, leading to aberrantbag-of-marbles(bam) expression, resulting in faulty differentiation and loss of GSCs. Additionally,sakurais necessary for normal piwi-interacting RNAs (piRNAs) levels and for proper localization of Ool8 RNA-binding protein (Orb) in developing oocytes. We identified Ovarian Tumor (Otu) as protein binding partner of Sakura, and we found that loss ofotuphenocopies loss ofsakurain ovaries. Thus, we identified Sakura as a crucial factor for GSC renewal and differentiation and oogenesis, and propose that Sakura and Otu function together in these processes.