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.sakurais also necessary for normal levels of piwi-interacting RNAs (piRNAs) levels and for female-specific splicing ofsex-lethal(sxl), a master regulator of sex identity determination. We identified Ovarian Tumor (Otu) as a protein binding partner of Sakura and found that loss ofotuphenocopies loss ofsakurain ovaries. Thus, we identify Sakura as a crucial factor for GSC renewal and differentiation and oogenesis, and propose that Sakura and Otu function together in these processes.