SRY, SOX9, and DAX1 expression patterns during human sex determination andgonadal development

SRY, SOX9, and DAX1 are key genes in human sex determination, by virtue of their associated male-to-female sex reversal phenotypes when mutated (SRY, SOX9) or over-expressed (DAX1). During human sex detennination, SRY is expr essed in 46,XY gonads coincident with sex cord formation, but also persists as nuclear protein within Sertoli cells at 18 weeks gestation. High-level SOX9 expression in the sex cords of the testis parallels that seen during m ouse development, however in humans, SOX9 transcripts also are detected in the developing ovary. Low-level DAX1 expression predates peak SRY expressio n by at least 10 days, and persists in Sertoli cells throughout the entire sex determination period. In Dosage Sensitive Sex reversal, the anti-testis properties of DAX1 over-expression could act prior to the peak effects of SRY and continue during the period of SOX9 expression. These findings highl ight expression differences for the SRY, SOX9, and DAX1 genes during sex de termination in humans and mice. These results provide a direct framework fo r future investigation into the mechanisms underlying normal and abnormal h uman sex determination. (C) 2000 Elsevier Science Ireland Ltd. All rights r eserved.