Sex determination, sex differentiation, and the Y chromosome—a mostly last quarter of the century effort

The nature of sex determination has long fascinated biologists, even Aristotle. In the mid-20th Century, Jost’s physiological studies established the primacy of the mammalian female body plan since early removal of the testes led to phenotypic females. The first morphological difference in gonads does not appear until they separate from the urogenital ridge. However, previous sexual differentiation has occurred, which could be related to very early expression of Sry, the sex-determining gene. This was first cloned in 1990 and experiments in mice rapidly proved its role in sex determination. It was found to regulate a number of downstream genes, including Sox 9. Multiple other genes were discovered which influenced primary sex determination and sexual differentiation. It was even found that gene expression was needed to maintain gonadal differentiation.