What is Sex Determination?
Unlike most organs whose fate is pre-determined, the gonad arises as a bipotential primordium that chooses to follow one of two developmental pathways. ‘Gonadal sex determination’ refers to the primary decision within gonadal cells to develop as a testis or ovary. Using genetic and systems biology approaches, we have investigated how Sry, the Y-linked sex-determining gene in mammals, functions to tip the bistable switch toward testis development. Questions currently at the top of our list are how the early gonad is initially established, how cells in the gonad community co-ordinate their fate, and how fate is maintained through epigenetic mechanisms.
Evolutionarily, sex determination is a very plastic process. As a comparative model for sex determination, we investigate the red-eared slider turtle, T. scripta. In this species, the temperature of egg incubation controls gonadal sex determination. We are very interested in determining whether there are underlying similarities in the transcriptional network between mice and turtles, and we have begun to unravel the longstanding puzzle of how temperature influences the genetic pathway.
Because of its unique bipotential nature, the gonad is an ideal model of organogenesis. We use the dramatic reorganization of gonadal tissue into either testis or ovary morphology as a model for the study of organogenesis. Based on our knowledge of testis and ovary development, we are exploring the ability of the testis and ovary to regenerate and repair after damage.
Other work in the lab focuses on the interactions between germ cells and somatic cells in testis and ovary development. We are particularly interested in the transition from primordial germ cell to oogonia or spermatogonial stem cell during ovary and testis development. In the testis, this transition involves a period of cell cycle arrest during which the pluripotent genome is stabilized. We are very interested in the signals from the somatic environment that control this critical developmental transition and in the process within germ cells.
Experimental approaches in the lab include the use of molecular and biochemical techniques, advanced imaging methods, null mutant mice, transgenic reporter mice, organ culture/tissue recombination assays, mouse genetics and genomics, and systems biology/bioinformatics tools.
Some Current Areas of Interest
- How does the gonad form? How is cell fate established, coordinated across the gonad field, and maintained during sex determination in the mouse? How is this process integrated with proliferation? Is the ECM involved?
- Which of the gonadal sex determination molecular and cell biology networks characterized in mice are conserved in red-eared slider turtles (Trachemys scripta elegans), where sex determination is regulated by temperature? What can this comparison tell us about evolution of sex determination?
- How is the heterogeneous expression of the RNA-binding protein DND1 involved in establishment of the spermatogonial stem cells in the testis?
- How is morphogenesis of the ovary related to the establishment of the primordial follicle pool around birth? What is the potential of the adult ovary to repair and recover from damage, and can this potential be harnessed in the clinic?
Meet the Team
Listen to Blanche giving radio interviews about sex determination
Radiolab Series on Gonads: RadioLab Presents: Gonads!
NPR “Morning Edition”: Half-Rooster/Half-Hen Helps Unlock Sex Mystery
Blanche presents “Early Development of the Ovary”
Capel, B. (2021, February 24). Early development of the ovary [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks.