In mammals, XY fetuses develop testes due to the action of the Y-linked testis determining gene Sry (sex-determining region, Y chromosome) and XX fetuses develop ovaries in its absence. SRY is a DNA binding protein, and is likely a transcription factor that regulates other genes in the sex determination pathway. The mammalian gonadal precursors (the genital ridges) are bipotential and capable of differentiating as either testes or ovaries. It is generally accepted that each genital ridge contains a complete set of lineage precursors that are capable of adopting an ovarian or testicular cell-type fate. This "common precursor" hypothesis is best viewed as a series of bipotential cell fate decisions within the four cell lineages that comprise the gonad: germ cells, connective tissue cells, steroid producing cells and supporting cells. The current model proposes that Sry expression in the genital ridge initiates testis development by directing supporting cell precursors to develop as Sertoli rather than granulosa cells and that the development of all other gonadal cell types is dependent on the differentiation of the supporting cell lineage. Besides Sertoli cell differentiation, two direct consequences of Sry expression are the initiation of a male specific pattern of cell proliferation and the induction of mesenchymal cell migration from the adjacent mesonephros into the developing testis, a process necessary for testis cord development.

Although it is clear that expression of Sry is the trigger for testis differentiation, the molecular mechanisms of Sry function remain an enigma. For example, no downstream SRY target genes have been unequivocally identified and the regulation of Sry expression remains largely unexplored. A number of genes involved in gonadogenesis and sex determination have been identified and characterized; however, the position and relationship of these genes within the pathway remain to be defined and many more genes remain to be discovered. For example, most of the identified genes are transcription factors and not effector molecules. Additionally, our understanding of the genes involved in ovary development is particularly thin. Our future studies will include investigating the regulation of Sry expression, defining the position and relationship of known genes and identifying new genes in the gonad differentiation and sex determination pathways, and exploring basic mechanisms of gonad differentiation.

Selected Publications