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Originally published in Science Express on 30 March 2006
Science 28 April 2006:
Vol. 312. no. 5773, pp. 596 - 600
DOI: 10.1126/science.1125691
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Reports

Retinoid Signaling Determines Germ Cell Fate in Mice

Josephine Bowles,1 Deon Knight,1 Christopher Smith,1* Dagmar Wilhelm,1 Joy Richman,1,3 Satoru Mamiya,4 Kenta Yashiro,4 Kallayanee Chawengsaksophak,5 Megan J. Wilson,1{dagger} Janet Rossant,5 Hiroshi Hamada,4 Peter Koopman1,2{ddagger}

Germ cells in the mouse embryo can develop as oocytes or spermatogonia, depending on molecular cues that have not been identified. We found that retinoic acid, produced by mesonephroi of both sexes, causes germ cells in the ovary to enter meiosis and inititate oogenesis. Meiosis is retarded in the fetal testis by the action of the retinoid-degrading enzyme CYP26B1, ultimately leading to spermatogenesis. In testes of Cyp26b1-knockout mouse embryos, germ cells enter meiosis precociously, as if in a normal ovary. Thus, precise regulation of retinoid levels during fetal gonad development provides the molecular control mechanism that specifies germ cell fate.

1 Division of Genetics and Developmental Biology, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia.
2 Australian Research Council Centre of Excellence in Biotechnology and Development, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia.
3 Department of Oral Health Science, Faculty of Dentistry, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
4 Division of Molecular Biology, Institute for Molecular and Cellular Biology, Osaka University, and Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation (JST), Osaka 565-0871, Japan.
5 Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.

* Present address: Faculty of Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.

{dagger} Present address: Biochemistry Department, University of Otago, Post Office Box 56, Dunedin, New Zealand.

{ddagger} To whom correspondence should be addressed. E-mail: p.koopman{at}imb.uq.edu.au

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