Formin Is Associated with Left-Right Asymmetry in the Pond Snail and the Frog

Davison, Angus; McDowell, Gary S.; Holden, Jennifer M.; Johnson, Harriet F.; Koutsovoulos, Georgios D.; Liu, M. Maureen; Hulpiau, Paco; Roy, Frans Van; Wade, Christopher M.; Banerjee, Ruby; Yang, Fengtang; Chiba, Satoshi; Davey, John W.; Jackson, Daniel J.; Levin, Michael; Blaxter, Mark L.

Abstract

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.

Citation

Davison, A., McDowell, G. S., Holden, J. M., Johnson, H. F., Koutsovoulos, G. D., Liu, M. M., …Blaxter, M. L. (2016). Formin Is Associated with Left-Right Asymmetry in the Pond Snail and the Frog. Current Biology, 26(5), 654-660. https://doi.org/10.1016/j.cub.2015.12.071

• Journal Article Type: Article
• Acceptance Date: Dec 29, 2015
• Online Publication Date: Feb 25, 2016
• Publication Date: Mar 7, 2016
• Deposit Date: Feb 26, 2016
• Publicly Available Date: Feb 26, 2016
• Journal: Current Biology
• Print ISSN: 0960-9822
• Electronic ISSN: 1879-0445
• Publisher: Cell Press
• Peer Reviewed: Peer Reviewed
• Volume: 26
• Issue: 5
• Pages: 654-660
• DOI: https://doi.org/10.1016/j.cub.2015.12.071
• Public URL: https://nottingham-repository.worktribe.com/output/775214
• Publisher URL: http://www.cell.com/current-biology/fulltext/S0960-9822(16)00056-7
• Related Public URLs: http://dx.doi.org/10.1016/j.cub.2015.12.071
• Additional Information: This article is maintained by: Elsevier; Article Title: Formin Is Associated with Left-Right Asymmetry in the Pond Snail and the Frog; Journal Title: Current Biology; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.cub.2015.12.071; Content Type: article; Copyright: Copyright © 2016 The Authors. Published by Elsevier Ltd.