Article | Published:

Retinoic acid signalling links left–right asymmetric patterning and bilaterally symmetric somitogenesis in the zebrafish embryo

Nature volume 435, pages 165171 (12 May 2005) | Download Citation

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Abstract

During embryogenesis, cells are spatially patterned as a result of highly coordinated and stereotyped morphogenetic events. In the vertebrate embryo, information on laterality is conveyed to the node, and subsequently to the lateral plate mesoderm, by a complex cascade of epigenetic and genetic events, eventually leading to a left–right asymmetric body plan. At the same time, the paraxial mesoderm is patterned along the anterior–posterior axis in metameric units, or somites, in a bilaterally symmetric fashion. Here we characterize a cascade of laterality information in the zebrafish embryo and show that blocking the early steps of this cascade (before it reaches the lateral plate mesoderm) results in random left–right asymmetric somitogenesis. We also uncover a mechanism mediated by retinoic acid signalling that is crucial in buffering the influence of the flow of laterality information on the left–right progression of somite formation, and thus in ensuring bilaterally symmetric somitogenesis.

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Acknowledgements

We thank T. Tsukui, H. Takeda and A. Smolka for sharing reagents; N. Hirokawa and P. Dollé for sharing results before publication; C. Kintner for helpful suggestions; all members of the laboratory for discussions; I. Dubova for help with fish procedures; C. Callol, T. Chapman, H. Kawakami and M. Sugii for technical assistance; and M.-F. Schwarz for help in the preparation of this manuscript. A.R. and C.R.-E. are partly supported by postdoctoral fellowships from Fundación Inbiomed, Spain. This study was funded by the NIH, the Human Frontier Science Program, and the G. Harold and Leila Y. Mathers Charitable Foundation.

Author information

Author notes

    • Yasuhiko Kawakami
    •  & Ángel Raya

    *These authors contributed equally to this work

Affiliations

  1. Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA

    • Yasuhiko Kawakami
    • , Ángel Raya
    • , R. Marina Raya
    • , Concepción Rodríguez-Esteban
    •  & Juan Carlos Izpisúa Belmonte

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Competing interests

The authors declare that they have no competing financial interests.

Corresponding author

Correspondence to Juan Carlos Izpisúa Belmonte.

Supplementary information

Word documents

  1. 1.

    Supplementary Figures

    Contains three Supplementary Figures, S1-S3 and additional references. Supplementary Figure S1 details the H+/K+-ATPase α immunoreactivity in zebrafish embryos. Supplementary Figure S2 shows the alterations in somitogenesis after inhibition of FGF and/or Wnt signalling. Supplementary Figure S3 details the expression of RA receptors in the zebrafish embryo.

  2. 2.

    Supplementary Table S1

    Left-right bias of asymmetric somitogenesis.

  3. 3.

    Supplementary Methods

    This contains additional details of the methods used in our study.

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DOI

https://doi.org/10.1038/nature03512

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