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Sex Determination & Gonadal Development
About this Laboratory
Disorders of sex development (DSDs), formerly intersex, are congenital conditions where development of chromosomal, gonadal, or anatomical sex is atypical. Our aim is to identify genes causing DSDs, and the molecular mechanisms underlying testis and ovary formation in the embryo. Approaches include human genetics, molecular, cell and developmental biology.
Related to Research Themes
Current Research
ATR-X syndrome & gonadal development - The ATR-X syndrome, an X-linked recessive developmental disorder affecting males, belongs to a growing list of disorders of sex development (DSD) which affect 1% of all newborns. Clinical features include mental retardation, alpha-thalassemia and skeletal and genital abnormalities. The focus of our work is to investigate the role of ATRX in gonadal development.
Genetic mechanisms underlying hypospadias - Hypospadias is one of the most common birth defects in humans affecting 1 in 250 boys in which the opening of the urethra is not at the end of the penis but along the shaft. We are exploring the genetic mechanisms underlying hypospadias by the generation of mouse models.
Identification of novel genes required for gonadal development - Our aim is to identify the underlying molecular and cellular events that cause human disorders of sexual development. As one approach, we are undertaking an ENU mutagenesis screen to identify novel genes involved in gonad development. We have identified several mutant strains affecting testis development which are currently under investigation.
- SOX9, Fgfr2 & testis development - We have shown that SOX9 and FGFR2 are key proteins during male sex determination. To identify the molecular pathways that SOX9 and FGFR2 act through, we are undertaking gene/protein expression analyses in Sox9 and Fgfr2 knockout gonads. We are also exploring the function of FGFR2 after the sex determination phase.
Discovering new genes responsible for DSDs - Our project aims to identify new genetics factors involved in rare disorders of human gonadal development using Array Comparative Genomic Hybridisation (CGH).
Wnt/β-catenin, SOX signaling & sex determination - While male and female gonadal development have been considered as independent, sex determination is regulated by opposing signals, (XY) tipped toward maleness by the presence of SRY. In females R-Spondin 1 (a Wnt agonist) is the earliest driving force. Using cell and molecular biology techniques, this project aims to understand the mechanisms of action of these two opposing pathways.