A MALE-SPECIFIC ROLE FOR SOX9 IN VERTEBRATE SEX DETERMINATION

Mutation analyses of patients with campomelic dysplasia, a bone dysmor phology and XY sex reversal syndrome, indicate that the SRY-related ge ne SOX9 is involved in both skeletal development and sex determination . To clarify the role SOX9 plays in vertebrate sex determination, we h ave investigated its expression during gonad development in mouse and chicken embryos, In the mouse, high levels of Sox9 mRNA were found in male (XY) but not female (XX) genital ridges, and were localised to th e sex cords of the developing testis, Purified fetal germ cells lacked Sox9 expression, indicating that Sox9 expression is specific to the S ertoli cell lineage, Sex specificity of SOX9 protein expression was co nfirmed using a polyclonal antiserum, The timing and cell-type specifi city of Sox9 expression suggests that Sox9 may be directly regulated b y SRY, Male-specific expression of cSOX9 mRNA during the sex determina tion period was also observed in chicken genital ridges. The conservat ion of sexually dimorphic expression in two vertebrate classes which h ave significant differences in their sex determination mechanisms, poi nts to a fundamental role for SOX9 in testis determination in vertebra tes. Sox9 expression was maintained in the mouse testis during fetal a nd adult life, but no expression was seen at any stage by in situ hybr idisation in the developing ovary, Male-specific expression was also o bserved in the cells surrounding the Mullerian ducts and in the epidid ymis, and expression in both sexes was detected in the developing coll ecting ducts of the metanephric kidney, These results suggest that SOX 9 may have a wider role in the development of the genitourinary system .