Sex-specific development of the gonad stem cell systems regulated by Doublesex Homologs of Drosophila Doublesex (Dsx), the Dsx-Mab3 Related Transcription Factors (DMRTs), are now known to control gonad sexual dimorphism across the animal kingdom, from planaria and water fleas, to worms, flies, mice and man. Male patients with deletions in the region of chromosome 9p22, and including DMRT's 1-3, exhibit disorders of the genitalia and gonads including ovotestes, indicating that DMRTs are essential for male gonad development in humans. Given the universal nature of DMRT involvement in gonad sexual dimorphism, a key question becomes how do these transcription factors regulate this process and what are their target genes? Here we propose to study these questions using both genomic and developmental approaches. In particular, a developmental process of high interest is in the development of the male and female stem cell systems. In mammals, this process is highly dimorphic as the testis has a stem cell system but the ovary does not. However, in many animals, both the ovary and the testis have stem cell system since both sexes need to produce large numbers of gametes for an extended period of life. These stem cell systems are also highly dimorphic between the sexes. Further, gonads of many organisms have a somatic stem cell (SSC) population in addition to the germline stem cells (GSCs), and the SSCs produce differentiating daughter cells that nurture the developing gametes. Here, we propose to study how Dsx acts to control two key aspects of the male and female stem cell systems, the male and female SSCs and the niche environments that control them.
The same homologous transcription factors, the DMRTs, control sex-specific development of the gonads across the animal kingdom. The goal of this proposal is to understand the targets by which these factors act to control sex-specific development, focusing on the formation of the male and female gonad stem cell systems.
