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)

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Lovell-Badge group

Dr Robin Lovell-Badge

Robin Lovell-Badge

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