The Genetic Network Directing Germline Sex Determination

A central aspect of reproduction is the proper development and sex determination of germ cells, but the underlying molecular mechanisms remain poorly understood. Our previous work identified an evolutionarily conserved histone reader PHD Finger Protein 7 (Phf7) as a critical regulator of male germline sex determination in Drosophila. Phf7 is associated with a remarkable array of sex-specific phenotypes including the ability to induce germline sex reversal. This discovery has opened numerous new windows to investigate the network of genes responsible for establishing important development decisions in the germline. In this research proposal, we outline our plans to use molecular and genetic approaches to investigate how Phf7 acts and is regulated at the molecular level, as well as to use Phf7 as a starting point to identify additional pathways and genes that are involved in germline development and sex determination. These intertwined efforts will shed light on fundamental mechanisms of germline biology. More importantly, our long-term goal is to eventually extend our work into human fertility. We have already found that the human homolog of Phf7 exhibits strong expression bias in the testis, much like in Drosophila. The human gene can also functionally replace the Drosophila counterpart, indicating that these molecules are indeed functional orthologs of each other. We believe our work in Drosophila will provide significant ground work that will allow us to develop new schemes in diagnosing and treating human infertility.

Project ID:PA10308-0434
External Project ID:MOST103-2311-B182-002