A critical aspect of gonad development is the formation of the male and female gonad stem cell niches. Both germline and somatic stem cells are required for continuous production of differentiated progeny for gametogenesis, while their surrounding microenvironments, or niches, control gonad stem cell division, maintenance, and their transition into differentiation. However, gonad stem cells and their niches are very differen in males and females, with distinct regulatory control and very different outcomes (sperm vs. eggs). Further, in some species, such as mammals, a clear stem cell population exists only in males, but not in females, resulting in a more limited reproductive potential in females. This proposal aims to understand the mechanisms governing sex-specific development of the gonad stem cell niche. It addresses fundamental aspects of the biology of sex determination that also have clear implications for stem cell biology and human reproductive health. Although the mechanisms that initiate sex determination vary tremendously in different animal species, it is now appreciated that a single family of transcription factors, the Doublesex, Mab3 Related Transcription Factors (DMRTs), controls sexual dimorphism in the gonads of most or all animal species, including flies and humans. How these transcription factors dictate the differences between male and female gonad stem cell niches is not yet understood. In this proposal, we will investigate how the founding member of the DMRT family, Drosophila doublesex (dsx), controls sexual dimorphism in the gonad stem cell niche.
Males and females differ in their development in fascinating ways, yet if these sex-specific programs are not executed correctly, this leads to infertility and other Disorders of Sexual Development. The Doublesex, Mab3 Related Transcription Factors (DMRTs) are now known to be important for sex-specific development in most or all animals, including flies and humans, and we will use the power of the Drosophila system to study these conserved sexual regulators.
