tudor-domain containing protein 5-primepromotes male sexual identity in theDrosophilagermline and is repressed in females bySex lethal

AbstractFor sexually reproducing organisms, production of male or female gametes depends on specifying the correct sexual identity in the germline. InD. melanogaster, Sex lethal(Sxl) is the key gene that controls sex determination in both the soma and the germline, but how it does so in the germline is unknown, other than that it is different than in the soma. We conducted an RNA expression profiling experiment to identify direct and indirect germline targets of Sxl specifically in the undifferentiated germline. We find that, in these cells,Sxlloss does not lead to a global masculinization observed at the whole-genome level. In contrast,Sxlappears to affect a discrete set of genes required in the male germline, such asPhf7. We also identifytudor domain containing protein 5-prime(tdrd5p) as a target for Sxl regulation that is important for male germline identity.tdrd5pis repressed by Sxl in female germ cells, but is highly expressed in male germ cells where it promotes proper male fertility and germline differentiation. Additionally, Tdrd5p localizes to cytoplasmic granules with some characteristics of RNA Processing (P-) Bodies, suggesting that it promotes male identity in the germline by regulating post-transcriptional gene expression.Author summaryLike humans, all sexually reproducing organisms require gametes to reproduce. Gametes are made by specialized cells called germ cells, which must have the correct sexual identity information to properly make sperm or eggs. In fruit flies, germ cell sexual identity is controlled by the RNA-binding protein Sxl, which is expressed only in females. To better understand howSxlpromotes female identity, we conducted an RNA expression profiling experiment to identify genes whose expression changes in response to the loss ofSxlfrom germ cells. Here, we identifytudor domain containing protein 5-prime (tdrd5p), which is expressed 17-fold higher in ovaries lackingSxlcompared to control ovaries. Additionally,tdrd5pplays an important role in males as male flies that are mutant for this gene cannot make sperm properly and thus are less fertile. Moreover, we find thattdrd5ppromotes male identity in the germline, as several experiments show that it can shift the germ cell developmental program from female to male. This study tells us thatSxlpromotes female identity in germ cells by repressing genes, liketdrd5p, that promote male identity. Future studies into the function oftdrd5pwill provide mechanistic insight into how this gene promotes male identity.