The Mammalian Sex Determination Laboratory
The main research interest of our lab is to understand, at the molecular level, how sex is determined during embryonic development, i.e., how does an embryo develop into either a male or a female.
In mammals, sex determination is genetically driven with XY individuals developing as males and XX individuals developing as females. However, if the process of sex determination is impaired, patients can appear as XY females or XX males (sex reverse). These are all classified as patients with Disorders of Sex Development (DSD), with a prevalence of 1: 2500-4000 newborns.
During embryonic development, the gonads initially develop as a bipotential organ and it is the activity of several key transcription factors that directs them to develop into either testes or ovaries. In the lab, we use the mouse as a model system and are interested in understanding the regulation of these key transcription factors and how these interact with each other.
We employ cutting-edge techniques to address these questions including CRISPR/Cas9 genome editing, transgenic mice production, advanced sequencing techniques as well as microscopy and molecular biology.
In addition, we utilize both mouse and human Embryonic Stem Cells and develop differentiation protocols towards gonadal cell types in order to study sex determination in an in-vitro context.
- Gonen N., Futtner CR., Wood S., Garcia-Moreno AS., Salamone IM., Samson SC., Sekido R., Poulat F., Maatouk DM., Lovell-Badge R.Sex Reversal Following Deletion of a Single Distal Enhancer of Sox9. Science 2018 Jun 29; 360 (6396):1469-1473
- Gonen N., Quinn A., O'Neill HC., Koopman P., Lovell-Badge R. Normal Levels of Sox9 Expression in the Developing Mouse Testis Depend on the TES/TESCO Enhancer, but This Does Not Act Alone. PLoS Genet. 2017 Jan 3;13(1)
- Gonen N. and Assaraf YG. The obligatory intestinal folate transporter PCFT (SLC46A1) is regulated by nuclear respiratory factor 1 (NRF-1). J. Biol. Chem. 2010 Oct 29; 285(44): 33602-13.