Sex Determination and Gonadal Development

Sex Determination and Gonadal Development Research Group

Research Group Head

3-D-model-testis-cordsIntersex variations (also referred to as Disorders of Sex Development), are congenital conditions where development of chromosomal, gonadal, or anatomical sex is atypical. Intersex variations encompass a wide range of conditions, including hypospadias (abnormal urinary opening in males), gonadal dysgenesis (underdeveloped or imperfectly formed gonads), and atypical genitalia and sex reversal (i.e. a congenital inconsistency between a person’s gonads and their phenotype).  Our aim is to identify genes causing intersex variations, and the molecular mechanisms underlying testis and ovary formation in the embryo. We hope to apply this knowledge to improve diagnosis of intersex variations. Approaches include human genetics, as well as molecular, cell and developmental biology.

Related Links

Research Projects

Research Group

Selected publications

  • Ono M, Harley V (2013) Disorders of sex development: new genes, new concepts. Nature Reviews Endocrinology 9(2):79-91.

  • Ludbrook L, Bernard P, Bagheri-Fam S, Sekido R, Wilhelm D, Lovell-Badge R, Harley VR (2012) Excess DAX1 leads to XY ovotesticular DSD in mice by inhibiting Sf1 activation of the testis enhancer of SOX9. Endocrinology 153:1948-1958.

  • Bernard P, Ryan J, Sim H, Czech DP, Sinclair AH, Koopman P, Harley VR (2012) Wnt signaling in ovarian development inhibits Sf1 activation of Sox9 via the Tesco enhancer. Endocrinology 153:901-912.

  • Bagheri-Fam S, Argentaro A, Svingen T, Combes A, Sinclair A, Koopman P, Harley VR (2011) Defective survival of proliferating Sertoli cells and androgen receptor function in a mouse model of the ATR-X syndrome. Human Molecular Genetics 20:2213-2224.

  • Knower KC, Kelly S, Ludbrook LM, Bagheri-Fam S, Sim H, Bernard P, Sekido R, Lovell-Badge R, Harley VR (2011) Failure of SOX9 regulation in 46XY disorders of sex development with SRY, SOX9 and SF1 mutations. PLoS One 6:e17751.

  • Sutton E, Hughes J, White S, Sekido R, Tan J, Arboleda V, Rogers N, Knower K, Rowley L, Eyre H, Rizzoti K, McAninch D, Goncalves J, Slee J, Turbitt E, Bruno D, Bengtsson H, Harley V, Vilain E, Sinclair A, Lovell-Badge R, Thomas P (2011) Identification of SOX3 as an XX male sex reversal gene in mice and humans. Journal of Clinical Investigation 121:328-341.

  • Harley VR, Layfield S, Mitchell CL, Forwood JK, John AP, Briggs LJ, McDowall SG, Jans DA (2003) Defective importin  recognition and nuclear import of the sex determining factor SRY are associated with XY sex reversing mutations. Proceedings of the National Academy of Sciences (USA) 100:7045-7050.

  • Harley VR, Jackson DI, Hextall PJ, Hawkins JR, Berkovitz GD, Sockanathan S, Lovell-Badge R, Goodfellow PN (1992) DNA-binding activity of recombinant SRY from normal males and XY females. Science 255:453-457.