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Female development in mammals is regulated by Wnt-4 signalling

Author

Listed:
  • Seppo Vainio

    (The BioLabs, Harvard University
    Faculties of Science and Medicine, University of Oulu)

  • Minna Heikkilä

    (Faculties of Science and Medicine, University of Oulu)

  • Andreas Kispert

    (The BioLabs, Harvard University
    MPI-Institut fr Immunobiologie, Abteilung fr Molekulare Embryologie)

  • Norman Chin

    (The BioLabs, Harvard University)

  • Andrew P. McMahon

    (The BioLabs, Harvard University)

Abstract

In the mammalian embryo, both sexes are initially morphologically indistinguishable: specific hormones are required for sex-specific development. Müllerian inhibiting substance and testosterone secreted by the differentiating embryonic testes result in the loss of female (Müllerian) or promotion of male (Wolffian) reproductive duct development, respectively. The signalling molecule Wnt-4 is crucial for female sexual development. At birth, sexual development in males with a mutation in Wnt-4 appears to be normal; however, Wnt-4-mutant females are masculinized—the Müllerian duct is absent while the Wolffian duct continues to develop. Wnt-4 is initially required in both sexes for formation of the Müllerian duct, then Wnt-4 in the developing ovary appears to suppress the development of Leydig cells; consequently, Wnt-4-mutant females ectopically activate testosterone biosynthesis. Wnt-4 may also be required for maintenance of the female germ line. Thus, the establishment of sexual dimorphism is under the control of both local and systemic signals.

Suggested Citation

  • Seppo Vainio & Minna Heikkilä & Andreas Kispert & Norman Chin & Andrew P. McMahon, 1999. "Female development in mammals is regulated by Wnt-4 signalling," Nature, Nature, vol. 397(6718), pages 405-409, February.
    • Handle: RePEc:nat:nature:v:397:y:1999:i:6718:d:10.1038_17068
    DOI: 10.1038/17068
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    Cited by:

    1. Alicia Hurtado & Irene Mota-Gómez & Miguel Lao & Francisca M. Real & Johanna Jedamzick & Miguel Burgos & Darío G. Lupiáñez & Rafael Jiménez & Francisco J. Barrionuevo, 2024. "Complete male-to-female sex reversal in XY mice lacking the miR-17~92 cluster," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    2. Jacek Z Kubiak & Jacek Z Kubiak & Malgorzata Kloc & Malgorzata Kloc & Rafal P Piprek, 2020. "History of The Research on Sex Determination," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 25(3), pages 19104-19112, February.
    3. Steven C Munger & Anirudh Natarajan & Loren L Looger & Uwe Ohler & Blanche Capel, 2013. "Fine Time Course Expression Analysis Identifies Cascades of Activation and Repression and Maps a Putative Regulator of Mammalian Sex Determination," PLOS Genetics, Public Library of Science, vol. 9(7), pages 1-17, July.

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