Formin Is Associated with Left-Right Asymmetry in the Pond Snail and the Frog
This is another fascinating paper showing how little we know about the most basic questions, including ‘symmetry-breaking’ during animal development.
Highlights
Animals tend to be outwardly symmetric but internally are asymmetric
Unlike other animals, snails show inherited variation in asymmetry
We found that both snails and frogs use a common gene to define left and right
Asymmetry is probably an ancient and conserved property of cells and animals
Summary
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 signaling of Nodal, downstream of symmetry breaking, may be an ancestral feature of the Bilateria [ 1, 2 ]. 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 overexpression by microinjection of formin has a chirality-randomizing effect in early (pre-cilia) embryos. Contrary to expectations based on existing models [ 35 ], 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 [ 6, 7 ], together these results are consistent with the view that animals with diverse body plans may derive their asymmetries from the same intracellular chiral elements [ 8 ].
