Davison, Angus and McDowell, Gary S. and Holden, Jennifer M. and Johnson, Harriet F. and Koutsovoulos, Georgios D. and Liu, M. Maureen and Hulpiau, Paco and Roy, Frans Van and Wade, Christopher M. and Banerjee, Ruby and Yang, Fengtang and Chiba, Satoshi and Davey, John W. and Jackson, Daniel J. and Levin, Michael and Blaxter, Mark L.
Formin is associated with left-right asymmetry in the pond snail and the frog.
While components of the pathway that establishes left-right asymmetry have been identified in diverse animals, from vertebrates to flies, it is striking that the genes involved in the first symmetry-breaking step remain wholly unknown in the most obviously chiral animals, the gastropod snails. Previously, research on snails was used to show that left-right signalling of Nodal, downstream of symmetry-breaking, may be an ancestral feature of the Bilateria. Here we report that a disabling mutation in one copy of a tandemly duplicated, diaphanous-related formin is perfectly associated with symmetry-breaking in the pond snail. This is supported by the observation that an anti-formin drug treatment converts dextral snail embryos to a sinistral phenocopy, and in frogs, drug inhibition or over-expression by microinjection of formin has a chirality-randomizing effect in early (pre-cilia) embryos. Contrary to expectations based on existing models, we discovered asymmetric gene expression in 2 and 4 cell snail embryos, preceding morphological asymmetry. As the formin-actin filament has been shown to be part of an asymmetry-breaking switch in vitro, together these results are consistent with the view that animals with diverse bodyplans may derive their asymmetries from the same intracellular chiral elements.
Actions (Archive Staff Only)