MRC National Institute for Medical Research, London
Science for Health
Robin Lovell-Badge group
Sex, stem cells and decisions of cell fate
Embryo development relies on cells making choices about which cell type to become and whether to divide, move or die. During the process of sex determination, cells of the early gonad have an additional choice to make: to become cells typical of testes or ovaries. In mammals this usually depends on the presence or absence of the Y chromosome (males are XY, females XX). This is due to just one gene on the Y, termed Sry, which encodes a transcription factor. SRY contains an HMG box type of DNA binding domain, also present in proteins encoded by the Sox gene family.
We use a wide range of techniques to explore how SRY and other factors act to initiate and then maintain testis and ovary differentiation. Mice are our main experimental model, and we study the chick for evolutionary comparisons since the initial trigger is different, but downstream effectors are probably the same. Our work informs the human situation, which when it goes wrong leads to devastating physiological and social consequences for affected individuals.
We also study stem cell types, including pluripotent stem cells from very early embryos (ES cells) or after reprogramming from adult cells (iPS cells), and multipotent stem cells from the developing and adult central nervous system and pituitary. Certain Sox genes are critical for self-renewal and to confer potential to stem cells. We therefore explore how these genes impact on cell fate choices, and how they might be exploited to aid the treatment of a range of clinical problems, such as stroke and cancer.
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GFP expression driven by a testis-specific enhancer of Sox9 in transgenic mice
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Pituispheres contain progenitors expressing SOX2 (green) and S100 protein (blue), able to differentiate into hormone-producing cells (green)
Selected publications
- Uhlenhaut NH, Jakob S, Anlag K, Eisenberger T, Sekido R, Kress J, Treier A-C, Klugmann C, Klasen C, Holter NI, Riethmacher D, SchG, Cooney AJ, Lovell-Badge R and Treier M (2009)
Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation.
Cell 139, 1130-1142 PubMed abstract - Fauquier, T; Rizzoti, K; Dattani, M; Lovell-Badge, R and Robinson, ICAF (2008)
SOX2-expressing progenitor cells generate all of the major cell types in the adult mouse pituitary gland.
Proceedings of the National Academy of Sciences of the United States of America 105, 2907-2912 PubMed abstract - Sekido, R and Lovell-Badge, R (2008)
Sex determination involves synergistic action of SRY and SF1 on a specific Sox9 enhancer.
Nature 453, 930-934 PubMed abstract
Our research themes
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