Article

A Nodal-independent and tissue-intrinsic mechanism controls heart-looping chirality

  • Nature Communications 4, Article number: 2754 (2013)
  • doi:10.1038/ncomms3754
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Abstract

Breaking left–right symmetry in bilateria is a major event during embryo development that is required for asymmetric organ position, directional organ looping and lateralized organ function in the adult. Asymmetric expression of Nodal-related genes is hypothesized to be the driving force behind regulation of organ laterality. Here we identify a Nodal-independent mechanism that drives asymmetric heart looping in zebrafish embryos. In a unique mutant defective for the Nodal-related southpaw gene, preferential dextral looping in the heart is maintained, whereas gut and brain asymmetries are randomized. As genetic and pharmacological inhibition of Nodal signalling does not abolish heart asymmetry, a yet undiscovered mechanism controls heart chirality. This mechanism is tissue intrinsic, as explanted hearts maintain ex vivo retain chiral looping behaviour and require actin polymerization and myosin II activity. We find that Nodal signalling regulates actin gene expression, supporting a model in which Nodal signalling amplifies this tissue-intrinsic mechanism of heart looping.

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Acknowledgements

We thank the ZF-Models screen consortium for facilitating the forward genetic screen and Jacqueline Deschamps for critical reading of the manuscript. This work was supported by the Research Council for Earth and Life Sciences (ALW) with financial aid from the Netherlands Organization for Scientific Research (NWO; grant 864.08.009).

Author information

Author notes

    • Anne Karine Lagendijk
    •  & Kelly Smith

    Present address: Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland 4072, Australia

    • Suma Choorapoikayil

    Present address: Université Montpellier II, 34095 Montpellier, Cedex 5, France

Affiliations

  1. Hubrecht Institute-KNAW and University Medical Center Utrecht, 3584CT Utrecht, The Netherlands

    • Emily S. Noël
    • , Manon Verhoeven
    • , Anne Karine Lagendijk
    • , Federico Tessadori
    • , Kelly Smith
    • , Suma Choorapoikayil
    • , Jeroen den Hertog
    •  & Jeroen Bakkers
  2. Interuniversity Cardiology Institute of the Netherlands, 3511GC Utrecht, The Netherlands

    • Jeroen Bakkers

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Contributions

E.S.N. and J.B. designed the study, discussed the results and wrote the manuscript. E.S.N. performed the experiments and analysed the data. M.V. identified the sfw mutant. F.T., S.C. and J.d.H. contributed to the heart explant study. A.K.L. and K.S. contributed the tnnt2a mutant data.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Jeroen Bakkers.

Supplementary information

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    Supplementary Information

    Supplementary Figures S1-S7 and Supplementary Tables S1-S3

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