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We are studying the specification and differentiation of the male germ line, with the aims of identifying genes involved in testicular and childhood cancers and male infertility, developing new approaches to transgenic animal production, identification of new targets for pest control, reprogramming germ cells for applications in biotechnology, and formulating strategies for enhancing or suppressing fertility. We have discovered two signalling pathways that control the decision of germ cells to follow the spermatogenic or the oogenic pathway. These involve retinoic acid, which acts in the fetal ovary to stimulate germ cell entry into meiosis and hence oogenesis, and FGF9, which acts in the developing testis to suppress entry into meiosis and promote spermatogenesis. We also find that nodal signalling plays a critical role in balancing differentiation and proliferation in fetal male germ cells – a finding with profound implications for male fertility and testis cancer. Key TechnologiesMicroarray screening, gene expression studies, derivation of stem cell populations, in-vitro differentiation of ES cells, transgenic mouse production, gene knockout studies. Key publicationsBowles, J, Knight, D, Smith, C, Wilhelm, D, Richman, J, Mamiya, S, Yashiro, K, Chawengsaksophak, K, Wilson, MJ, Rossant, J, Hamada, H and Koopman, P (2006). Retinoid signaling determines germ cell fate in mice. Bowles, J and Koopman, P (2007). Retinoic acid, meiosis and germ cell fate in mammals.Invited review. Bowles, J, Feng, C-W, Spiller, C, Davidson, T-L, Jackson, A and Koopman, P (2010). FGF9 suppresses meiosis and promotes male germ cell fate in mice. Rolland, AD, Lehmann, KP, Johnson, KJ, Gaido, KW and Koopman, P (2011). Uncovering gene regulatory networks during mouse fetal germ cell development. |
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