The Molecular Genetics of Sry and its Role in Mammalian Sex Determination [and Discussion]

The process of sex determination, by which is meant the decision as to whether an embryo develops as a male or a female, is considered as a paradigm of how gene action can influence developmental fate. In mammals the decision is dependent on the action of the testis determining gene present on the Y chromosome, now known to be the gene Sry. Sry is expressed for only a brief period in the mouse embryo and must act to initiate rather than maintain the pathway of gene activity required for testis differentiation. It probably acts within cells of the supporting cell lineage to direct their differentiation into Sertoli cells, rather than the granulosa cells characteristic of the ovary. Other lineages in the gonad then follow the male pathway. The nature of the Sry transcript in the genital ridge of mice has been determined and compared with that from the human gene which is dramatically different. The expression of Sry has been carefully examined during the critical stages of genital ridge development and compared to the expression of a number of other genes involved in gonadal development and male development such as that for anti-Mullerian hormone. This has defined the period in which Sry must act to between 11 and 11.5 days post coitum. The expression of Sry has also been examined in cases of sex reversal in the mouse. There is a dependence on level of expression and extent of testicular differentiation that suggests thresholds for both the amount of SRY per cell and the number of cells expressing the gene. The SRY protein interacts with DNA through an HMG box type of DNA binding domain, however at present no definite target genes have been found. Progress on strategies to find such genes is discussed.