Letter | Published:

Nodal signalling is involved in left–right asymmetry in snails

Nature volume 457, pages 10071011 (19 February 2009) | Download Citation


Many animals display specific internal or external features with left–right asymmetry. In vertebrates, the molecular pathway that leads to this asymmetry uses the signalling molecule Nodal, a member of the transforming growth factor-β superfamily1, which is expressed in the left lateral plate mesoderm2, and loss of nodal function produces a randomization of the left–right asymmetry of visceral organs3,4. Orthologues of nodal have also been described in other deuterostomes, including ascidians and sea urchins5,6, but no nodal orthologue has been reported in the other two main clades of Bilateria: Ecdysozoa (including flies and nematodes) and Lophotrochozoa (including snails and annelids). Here we report the first evidence for a nodal orthologue in a non-deuterostome group. We isolated nodal and Pitx (one of the targets of Nodal signalling) in two species of snails and found that the side of the embryo that expresses nodal and Pitx is related to body chirality: both genes are expressed on the right side of the embryo in the dextral (right-handed) species Lottia gigantea and on the left side in the sinistral (left-handed) species Biomphalaria glabrata. We pharmacologically inhibited the Nodal pathway and found that nodal acts upstream of Pitx, and that some treated animals developed with a loss of shell chirality. These results indicate that the involvement of the Nodal pathway in left–right asymmetry might have been an ancestral feature of the Bilateria.

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Data deposits

Nodal, Pitx and hedgehog sequences of L. gigantea and B. glabrata are deposited at the EMBL-GenBank data libraries; accession numbers EU394708 and EU394707 (for nodal), EU797117 and EU797116 (for Pitx) and EU394706 and EU394705 (for hedgehog). In addition, a brachyury sequence of L. gigantea is deposited as accession number EU797118.


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We thank E. Begovic, E. E. Gonzales and I. Martínez-Solano for help collecting and fertilizing L. gigantea. A. Almeida helped with the drug experiments. D. R. Lindberg provided the Busycon pulleyi specimen. The NIAID Schistosomiasis Resource Center provided adults of B. glabrata. We thank M. Levine, D. R. Lindberg, P. Liu, M. Modrell, S. Nichols, M. Protas and J. Rehm for comments on the manuscript, and I. Hariharan for suggesting the experiments with rapamycin. C.G. was sponsored by a postdoctoral fellowship of the Ministerio de Educacion y Ciencia (Spain) and the Center for Integrative Genomics. N.H.P. is an Investigator of the Howard Hughes Medical Institute.

Author Contributions C.G. performed experiments; C.G. and N.H.P. designed experiments, collected and analysed data, and wrote the manuscript.

Author information


  1. Department of Molecular and Cell Biology,

    • Cristina Grande
    •  & Nipam H. Patel
  2. Department of Integrative Biology, and,

    • Cristina Grande
    •  & Nipam H. Patel
  3. Center for Integrative Genomics, University of California, Berkeley, California 94720-3200, USA

    • Cristina Grande
    •  & Nipam H. Patel


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Corresponding author

Correspondence to Nipam H. Patel.

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    Supplementary Information

    This file contains Supplementary Figures 1-5 with Legends, Supplementary Tables 1-3, Supplementary Methods and Supplementary Results

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