[Sex determination, it is all about timing]

Abstract

The sex of an individual is determined at the time of fertilization. The mother passes on one sex chromosome, the X chromosome, and the father transmits the second sex chromosome, X or Y. Thus, an XX embryo becomes a female, whereas an XY individual becomes a male. A process known as "primary sex determination" allows the bipotential gonad to become a testis or an ovary in XY and XX embryos, respectively. In 1990, the Sry gene, located on the Y chromosome, was found to be necessary and sufficient to induce the male developmental program. At this time, the scientific community thought that other genes involved in the process of sex determination would be rapidly identified. However, it took more than 30 years to identify the ovarian determining factor. This factor is one variant of WT1, denoted -KTS, which is required to induce ovarian development in XX mice and can prevent male development of the gonad when it is prematurely activated in XY embryos. Because the -KTS variant of WT1 acts very early during development, this discovery opens new avenues for research on ovarian development, as it happened for SRY for testis development. It will also lead to a better understanding of the regulatory gene networks implicated in many unresolved cases of sex development disorders.