Oral Presentation ESA-SRB Conference 2015

New regulators of mammalian sex determination and gonad development (#113)

Dagmar Wilhelm 1 , Raphael Rastetter 1 , Sean Wilson 1 , Simon Windley 1 , James Hughes 2 , Pierre Calvel 3 , Quenten Schwarz 4 , Serge Nef 3 , Paul Thomas 2
  1. Monash University, Clayton, VIC, Australia
  2. School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia
  3. Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland
  4. Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, South Australia, Australia

Disorders of sexual development (DSDs) are surprisingly common. They range from mild genital abnormalities to complete sex reversal. The cause of these problems is often a failure of the complex networks of gene regulation that drives the differentiation of testes and ovaries respectively. While recent data has significantly advanced our understanding of the molecular and cellular processes of testis and ovary differentiation, many DSDs still remain unexplained at the molecular level, suggesting that important factors remain to be discovered. Past studies have focussed on the discovery and characterization of genes that are sexually dimorphically expressed, based on the assumption that a factor involved in testis differentiation is not expressed in the ovary and vice versa. We have now identified genes that are expressed in both the developing testis and ovary, for which null mutation in mice surprisingly lead to a very specific gonadal phenotype. These knockout mice display male-to-female sex reversal as well as a failure or a delay in ovarian germ cell differentiation. These data highlight the fact that by limiting our investigations to sexually dimorphically expressed genes we might miss important regulators.