Dmrt1: a common thread in sex determination

Dmrt1 and its related genes play a key role in sex determination in a broad range of metazoan species. However, Dmrt1 has become dispensable for testis determination in mammals, and this function is instead carried out by Sry, which is a newly evolved gene found on the Y chromosome. Now, Peter Koopman and colleagues show that, even though its function is not normally required, Dmrt1 is able to drive female-to-male sex reversal in mice (p. 1083). The researchers show that the transgenic overexpression of Dmrt1 in XX mouse foetal gonads is able to induce testis formation. The resulting gonads exhibit typical testicular size and vascular patterning, and contain Sertoli cells that express the hallmark testis-determining gene Sox9. By contrast, the expression of ovarian markers is repressed and granulosa cells are absent. The researchers further show that this testis phenotype persists into adulthood; male internal and external reproductive organs develop, whereas female structures are absent. Together, these findings suggest that Dmrt1 has retained the ability to act as a sex-determining factor in mammals, highlighting a common thread in the evolution of sex-determination mechanisms in metazoans.