Letter | Published:

Transient activation of calcineurin is essential to initiate embryonic development in Xenopus laevis

Nature volume 449, pages 341345 (20 September 2007) | Download Citation

Abstract

At fertilization, an increase of cytosolic calcium ions (Ca2+) triggers various activation responses in animal eggs1,2. In vertebrates, these responses include exit from metaphase arrest in meiosis II (MII exit) and cortical remodelling initiated by cortical granule exocytosis. Although the essential requirement of Ca2+/calmodulin-dependent protein kinase II for inducing MII exit has been documented3, a role of the Ca2+/calmodulin-dependent protein phosphatase calcineurin in egg activation has not been investigated. Here we show, using cell-free extracts from unfertilized eggs of Xenopus laevis, that calcineurin is transiently activated immediately after Ca2+ addition to a concentration that induces MII exit. When calcineurin activation is inhibited, cyclin-dependent kinase 1 (Cdk1) inactivation by means of cyclin B degradation is prevented and sperm chromatin incubated in the extracts remains condensed. Similarly, if calcineurin is inhibited in intact eggs, MII exit on egg activation is prevented. In addition, the activation contraction4 in the cortex is suppressed whereas cortical granule exocytosis occurs. We further demonstrate that, when a high level of calcineurin activity is maintained after activation, growth of sperm asters is prevented in egg extracts and, consistently, migration of male and female pronuclei towards each other is hindered in fertilized eggs. Thus, both activation and the subsequent inactivation of calcineurin in fertilized eggs are crucial for the commencement of vertebrate embryonic development.

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Acknowledgements

We thank S. Mochida and T. Hunt for sharing their unpublished findings with us and all the laboratory members for discussions. We thank M. J. Lohka for critical reading of the manuscript. This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan to K.O. and T.K.

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Affiliations

  1. Laboratory of Cell and Developmental Biology, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan

    • Tomoko Nishiyama
    • , Takeo Kishimoto
    •  & Keita Ohsumi
  2. Department of Animal Resource Production, United Graduate School of Agricultural Science, Gifu University, Gifu 501-1193, Japan

    • Norio Yoshizaki

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Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.

Corresponding author

Correspondence to Keita Ohsumi.

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https://doi.org/10.1038/nature06136

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