Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Logo for

Science 312 (5773): 596-600

Copyright © 2006 by the American Association for the Advancement of Science

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}

Abstract: 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

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
STRA8-deficient spermatocytes initiate, but fail to complete, meiosis and undergo premature chromosome condensation.
M. Mark, H. Jacobs, M. Oulad-Abdelghani, C. Dennefeld, B. Feret, N. Vernet, C.-A. Codreanu, P. Chambon, and N. B. Ghyselinck (2008)
J. Cell Sci. 121, 3233-3242
   Abstract »    Full Text »    PDF »
Stabilization of {beta}-catenin in XY gonads causes male-to-female sex-reversal.
D. M. Maatouk, L. DiNapoli, A. Alvers, K. L. Parker, M. M. Taketo, and B. Capel (2008)
Hum. Mol. Genet. 17, 2949-2955
   Abstract »    Full Text »    PDF »
Stra8 and its inducer, retinoic acid, regulate meiotic initiation in both spermatogenesis and oogenesis in mice.
E. L. Anderson, A. E. Baltus, H. L. Roepers-Gajadien, T. J. Hassold, D. G. de Rooij, A. M. M. van Pelt, and D. C. Page (2008)
PNAS 105, 14976-14980
   Abstract »    Full Text »    PDF »
Modelling germ cell development in vitro.
A. J. Childs, P. T.K. Saunders, and R. A. Anderson (2008)
Mol. Hum. Reprod. 14, 501-511
   Abstract »    Full Text »    PDF »
Expression of Genes Associated with Retinoid Metabolism in the Trout Ovarian Follicle.
L. Levi, B. Levavi-Sivan, and E. Lubzens (2008)
Biol Reprod 79, 570-577
   Abstract »    Full Text »    PDF »
Oocytes in Newborn MRL Mouse Testes.
S. Otsuka, A. Konno, Y. Hashimoto, N. Sasaki, D. Endoh, and Y. Kon (2008)
Biol Reprod 79, 9-16
   Abstract »    Full Text »    PDF »
Expression of Stimulated by Retinoic Acid Gene 8 (Stra8) in Spermatogenic Cells Induced by Retinoic Acid: An In Vivo Study in Vitamin A-Sufficient Postnatal Murine Testes.
Q. Zhou, R. Nie, Y. Li, P. Friel, D. Mitchell, R. A Hess, C. Small, and M. D Griswold (2008)
Biol Reprod 79, 35-42
   Abstract »    Full Text »    PDF »
Activation of {beta}-catenin signaling by Rspo1 controls differentiation of the mammalian ovary.
A.-A. Chassot, F. Ranc, E. P. Gregoire, H. L. Roepers-Gajadien, M. M. Taketo, G. Camerino, D. G. de Rooij, A. Schedl, and M.-C. Chaboissier (2008)
Hum. Mol. Genet. 17, 1264-1277
   Abstract »    Full Text »    PDF »
Sdmg1 is a conserved transmembrane protein associated with germ cell sex determination and germline-soma interactions in mice.
D. Best, D. A. Sahlender, N. Walther, A. A. Peden, and I. R. Adams (2008)
Development 135, 1415-1425
   Abstract »    Full Text »    PDF »
Meiosis in oocytes: predisposition to aneuploidy and its increased incidence with age.
K. T. Jones (2008)
Hum. Reprod. Update 14, 143-158
   Abstract »    Full Text »    PDF »
Expression of Stimulated by Retinoic Acid Gene 8 (Stra8) and Maturation of Murine Gonocytes and Spermatogonia Induced by Retinoic Acid In Vitro.
Q. Zhou, Y. Li, R. Nie, P. Friel, D. Mitchell, R. M. Evanoff, D. Pouchnik, B. Banasik, J. R. McCarrey, C. Small, et al. (2008)
Biol Reprod 78, 537-545
   Abstract »    Full Text »    PDF »
Nanos2 suppresses meiosis and promotes male germ cell differentiation.
A. Suzuki and Y. Saga (2008)
Genes & Dev. 22, 430-435
   Abstract »    Full Text »    PDF »
Mechanism of asymmetric ovarian development in chick embryos.
Y. Ishimaru, T. Komatsu, M. Kasahara, Y. Katoh-Fukui, H. Ogawa, Y. Toyama, M. Maekawa, K. Toshimori, R. A. S. Chandraratna, K.-i. Morohashi, et al. (2008)
Development 135, 677-685
   Abstract »    Full Text »    PDF »
Dynamic Regulation of Mitotic Arrest in Fetal Male Germ Cells.
P. S. Western, D. C. Miles, J. A. van den Bergen, M. Burton, and A. H. Sinclair (2008)
Stem Cells 26, 339-347
   Abstract »    Full Text »    PDF »
SRY and the Standoff in Sex Determination.
L. DiNapoli and B. Capel (2008)
Mol. Endocrinol. 22, 1-9
   Abstract »    Full Text »    PDF »
Mature oocytes derived from purified mouse fetal germ cells.
T. Qing, H. Liu, W. Wei, X. Ye, W. Shen, D. Zhang, Z. Song, W. Yang, M. Ding, and H. Deng (2008)
Hum. Reprod. 23, 54-61
   Abstract »    Full Text »    PDF »
Loss of Wnt4 and Foxl2 leads to female-to-male sex reversal extending to germ cells.
C. Ottolenghi, E. Pelosi, J. Tran, M. Colombino, E. Douglass, T. Nedorezov, A. Cao, A. Forabosco, and D. Schlessinger (2007)
Hum. Mol. Genet. 16, 2795-2804
   Abstract »    Full Text »    PDF »
Retinoid Inactivation: Survival Factor for Male Germ Cells.
W. S. Blaner and C. L. Mendelsohn (2007)
Endocrinology 148, 4557-4559
   Full Text »    PDF »
Apoptotic Extinction of Germ Cells in Testes of Cyp26b1 Knockout Mice.
G. MacLean, H. Li, D. Metzger, P. Chambon, and M. Petkovich (2007)
Endocrinology 148, 4560-4567
   Abstract »    Full Text »    PDF »
Autonomous Regulation of Sex-Specific Developmental Programming in Mouse Fetal Germ Cells.
K. Iwahashi, H. Yoshioka, E. W Low, J. R McCarrey, R. Yanagimachi, and Y. Yamazaki (2007)
Biol Reprod 77, 697-706
   Abstract »    Full Text »    PDF »
Retinoic acid, meiosis and germ cell fate in mammals.
J. Bowles and P. Koopman (2007)
Development 134, 3401-3411
   Abstract »    Full Text »    PDF »
Eggs in the Nest.
K. Mayo, L. Jameson, and T. K. Woodruff (2007)
Endocrinology 148, 3577-3579
   Full Text »    PDF »
The Mysteries of Sexual Identity: The Germ Cell's Perspective.
J. Kimble and D. C. Page (2007)
Science 316, 400-401
   Abstract »    Full Text »    PDF »
In Vitro Gamete Derivation from Pluripotent Stem Cells: Progress and Perspective.
M. C. Nagano (2007)
Biol Reprod 76, 546-551
   Abstract »    Full Text »    PDF »
The small heterodimer partner is a gonadal gatekeeper of sexual maturation in male mice.
D. H. Volle, R. Duggavathi, B. C. Magnier, S. M. Houten, C. L. Cummins, J.-M. A. Lobaccaro, G. Verhoeven, K. Schoonjans, and J. Auwerx (2007)
Genes & Dev. 21, 303-315
   Abstract »    Full Text »    PDF »
Sex Determination and Gonadal Development in Mammals.
D. Wilhelm, S. Palmer, and P. Koopman (2007)
Physiol Rev 87, 1-28
   Abstract »    Full Text »    PDF »
Dppa2 and Dppa4 Are Closely Linked SAP Motif Genes Restricted to Pluripotent Cells and the Germ Line.
J. Maldonado-Saldivia, J. van den Bergen, M. Krouskos, M. Gilchrist, C. Lee, R. Li, A. H. Sinclair, M. A. Surani, and P. S. Western (2007)
Stem Cells 25, 19-28
   Abstract »    Full Text »    PDF »

ADVERTISEMENT
Click Me!

ADVERTISEMENT

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (pre-2008: Science's STKE. ISSN 1525-8882)