title: SRY, SOX9, and DAX1 expression patterns during human sex determination and gonadal development.
abstract: 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 determination, SRY is expressed 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 mouse development, however in humans, SOX9 transcripts also are detected in the developing ovary. Low-level DAX1 expression predates peak SRY expression 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 highlight expression differences for the SRY, SOX9, and DAX1 genes during sex determination in humans and mice. These results provide a direct framework for future investigation into the mechanisms underlying normal and abnormal human sex determination.
authors.affiliation: School of Biochemistry and Genetics, University of Newcastle upon Tyne, Newcastle upon Tyne, UK. nhanle@mednet.swmed.edu
authors.forename: N A
authors.initials: NA
authors.lastname: Hanley
authors.forename: D M
authors.initials: DM
authors.lastname: Hagan
authors.forename: M
authors.initials: M
authors.lastname: Clement-Jones
authors.forename: S G
authors.initials: SG
authors.lastname: Ball
authors.forename: T
authors.initials: T
authors.lastname: Strachan
authors.forename: L
authors.initials: L
authors.lastname: Salas-Cortés
authors.forename: K
authors.initials: K
authors.lastname: McElreavey
authors.forename: S
authors.initials: S
authors.lastname: Lindsay
authors.forename: S
authors.initials: S
authors.lastname: Robson
authors.forename: P
authors.initials: P
authors.lastname: Bullen
authors.forename: H
authors.initials: H
authors.lastname: Ostrer
authors.forename: D I
authors.initials: DI
authors.lastname: Wilson
mesh_terms: D000818:Animals; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000235:genetics*; D015870:Gene Expression; D006066:Gonads / Q000196:embryology; D006609:High Mobility Group Proteins / Q000235:genetics*; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D012097:Repressor Proteins; D055758:SOX9 Transcription Factor; D019849:Sex Determination Processes; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; C539965:NR0B1 protein, human; C539966:Nr0b1 protein, mouse; D009687:Nuclear Proteins; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; C527933:Sox9 protein, mouse; C497746:Sry protein, mouse; D014157:Transcription Factors