More than 27 years have passed since the discovery of Sry, the Y-chromosomal gene responsible for directing male development in eutherian mammals. This landmark discovery in 20th century molecular genetics opened the door to detailed study of how genetic pathways channel the development of the initially ambiguous embryonic gonads into testes and so generate males, while suppressing ovarian development.
In this talk, I will draw together current knowledge relating to how Sry activates it target gene Sox9 to set in train the events leading to Sertoli cell differentiation, in turn triggering a cellular cascade of events leading to testis formation. The unusual genetics and biology of Sry, and of gonadal development, have led to a number of curious idiosyncrasies, which I will also describe. Our current progress relating to the regulation and structure/function of Sry will be presented. Finally, I will describe efforts to gain a better understanding of the causes of disorders or differences of sex development (DSDs), a diverse group of conditions commonly associated with complex healthcare issues, impaired reproductive capacity, and gonadal cancer, and applying this knowledge to the diagnosis and clinical management of DSD, so as to improve outcomes for affected children and adults.