Investigating Germline Sex Determination

Investigating Germline Sex Determination Establishing sex-specific germ cell identity is critical for development of sperm and eggs and perpetuation of the species. Cells are initially specified as primordial germ cells (PGCs), and then germline sex determination establishes a male or female germline identity. While sex determination is understood in the somatic cells of some animals, how germline sexual identity is established is largely unknown. In most animals, germline sex determination is regulated by signals from the surrounding somatic gonad. However, in some animals, like humans and Drosophila, the germ cell’s sex chromosome constitution is also important. Thus, the sex of the soma and germline must match for proper gametogenesis to proceed. How somatic signals interface with germ cell autonomous cues to achieve proper sex determination is also unknown. Many aspects of germ cell identity are regulated at the post-transcriptional level. The RNA binding protein Sex lethal (Sxl) is activated in XX germ cells and is necessary and sufficient for germline sex determination in Drosophila, but little is known about how it acts to control this process. Further, a germ cell-specific transcriptional program must also be established in order for Sxl to influence this program in a sex-specific manner. Lastly, Sxl in the germline must combine with signals from the soma to determine germline sexual identity. Recently, we have made two important discoveries that illuminate these processes. First, an important signal from the soma that promotes male germline identity acts through the Jak/Stat pathway. As this pathway is also used to regulate development of the somatic gonad in both sexes, Sxl acts in female germ cells to block the Jak/Stat pathway and preserve female germline identity. Second, we have discovered a new tudor-domain protein, Tdrd5l, that is important for male identity in the germline and is a putative target for repression by Sxl in the female germline. Tdrd5l defines a novel germline granule, the “Tdrd5l body” and our preliminary data indicates that Tdrd5l regulates germline gene expression at the post-transcriptional level. We propose to use Tdrd5l as a model for understanding the regulation of gene expression in the germline and to investigate the mechanism of action of the “Tdrd5l body”.