Characterisation of novel gonadal targets of Sox9

Project description

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 are causative variants 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 testes compared to XX ovaries during development and down-regulated in sex-reversed XY ovaries ablated for Sox9. We will perform detailed expression profiling in XX and XY embryonic gonads of wild-type mice during the critical sex determination period of E11.5-E13.5, postnatally and at adult stages. We will also perform Sox9 ChIPseq on gonads and promoter/enhancer analyses, and screen DSD patients towards validation.