Characterisation of novel gonadal targets of Sox9

For the majority of Intersex cases the underlying genetic aetiology is unknown. In males Sox9 is a critical ‘hub’ gene involved in sexual development. We hypothesise that Sox9’s downstream targets are also essential for gonadal development and mutated in Intersex patients. By extensive data mining of gonadal microarrays, RNAseq, and SOX9 ChIPseq we have identified genes directly regulated by SOX9. These candidate genes are up regulated in XY mouse testis compared to XX ovaries during development and down regulated in sex reversed XY ovaries ablated for Sox9. We performed detailed expression profiling in XX and XY embryonic gonad of wild type mice during the critical sex determination period E11.5-E13.5, postnatally and at adult stages. We also performed SOX9 ChIPseq on gonads and promoter/enhancer analyses and screen DSD patients towards validation. Candidate target genes will be validated in cell culture and ex-vivo gonadal culture. 1. Rahmoun M, Lavery R, Laurent-Chabalier S, Bellora N, Philip G, Rossitto M, Symon A, Pailhoux E, Cammas F, Chung J, Murphy M, Bardwell V, Zarkower D, Boizet-Bonhoure B, Clair P, Harley V, Poulat F (2017). In mammalian foetal testes, SOX9 regulates transcription and splicing of its target genes by binding to genomic regions with conserved signatures. Nucleic Acids Research, 45(12):7191-7211