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. The <i>Drosophila</i> female germline serves as an excellent model for studying these regulatory mechanisms. Here, we report that a previously uncharacterized gene <i>CG14545</i>, which we named <i>sakura</i>, is essential for oogenesis and female fertility in <i>Drosophila</i>. Sakura is predominantly expressed in the ovaries, particularly in the germline cells, including GSCs. sakura null mutant female flies display rudimentary ovaries with germline-less and tumorous phenotypes, fail to produce eggs, and are completely sterile. The germline-specific depletion of sakura impairs Dpp/BMP signaling, leading to aberrant <i>bag-of-marbles</i> (<i>bam</i>) expression, resulting in faulty differentiation and loss of GSCs. sakura is also necessary for normal levels of piwi-interacting RNAs (piRNAs) levels and for female-specific splicing of <i>sex-lethal</i> (<i>sxl</i>), a master regulator of sex identity determination. We identified Ovarian Tumor (Otu) as a protein binding partner of Sakura and found that loss of <i>otu</i> phenocopies loss of <i>sakura</i> in 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.