The development of male germ cells back forward
sox evolution and functions

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 Technologies

Microarray screening, gene expression studies, derivation of stem cell populations, in-vitro differentiation of ES cells, transgenic mouse production, gene knockout studies.

Key publications

Bowles, 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.
Science 312: 596–600.

Bowles, J and Koopman, P (2007). Retinoic acid, meiosis and germ cell fate in mammals.Invited review.
Development 134: 3401–341.

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.
Developmental Cell 19: 440–449. (Commentary in Asian Journal of Andrology; Faculty of 1000 “Must read”; highlight in A-IMBN Research, Macmillan Science Communications).

Rolland, AD, Lehmann, KP, Johnson, KJ, Gaido, KW and Koopman, P (2011). Uncovering gene regulatory networks during mouse fetal germ cell development.
Biology of Reproduction 84: 790–800.