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Nodal signalling is involved in left–right asymmetry in snails

2008; Nature Portfolio; Volume: 457; Issue: 7232 Linguagem: Inglês

10.1038/nature07603

1476-4687

Cristina Grande, Nipam H. Patel,

Marine Biology and Ecology Research

The chirality (direction of coiling) of snail shells is an enduring biological puzzle. Cristina Grande and Nipam Patel now show that snail chirality is regulated by nodal, a gene well known for its role in vertebrate left-right asymmetry. Most animals are bilaterally symmetrical, but within that framework display varying amounts of left-right asymmetry. In vertebrates and other deuterostomes, the molecular pathway that leads to asymmetry utilizes the signalling molecule Nodal. Grande and Patel found orthologues (evolutionary equivalents) of Nodal and one of its targets, Pitx, in two species of snail, and show that loss of nodal disrupts shell coiling. This shows that the nodal signalling pathway is primitive for all bilaterians, and is not a particular feature of deuterostomes, as had been suspected. In vertebrates and other deuterostomes, the molecular pathway that leads to asymmetry utilizes the signalling molecule Nodal, a member of the TGF-β superfamily. But no orthologues of Nodal have been found in the other two great groups of bilaterians. This paper finds orthologues of nodal and one of its targets, Pitx, in two species of snail, and show that loss of nodal disrupts shell coiling. 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.