Failure of SOX9 regulation in 46XY disorders of sex development with SRY, SOX9 and SF1 mutations
Authors listKevin C Knower Sabine Kelly Louisa M Ludbrook Stefan Bagheri-Fam Helena Sim Pascal Bernard Ryohei Sekido Robin Lovell-Badge Vincent R Harley
In human embryogenesis, loss of SRY (sex determining region on Y), SOX9 (SRY-related HMG box 9) or SF1 (steroidogenic factor 1) function causes disorders of sex development (DSD). A defining event of vertebrate sex determination is male-specific upregulation and maintenance of SOX9 expression in gonadal pre-Sertoli cells, which is preceded by transient SRY expression in mammals. In mice, Sox9 regulation is under the transcriptional control of SRY, SF1 and SOX9 via a conserved testis-specific enhancer of Sox9 (TES). Regulation of SOX9 in human sex determination is however poorly understood.