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

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

doi:10.1016/j.cub.2015.12.071

Abstract

SummaryWhile 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 [3, 4, 5], 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].

Highlights

Bilaterian animals are more or less symmetrical about the midline that divides left and right, but internally most organs are asymmetric in location or shape
Given the importance of chiral patterning in the three bilaterian superphyla, Deuterostomia, Ecdysozoa, and Lophotrochozoa, a continuing problem is a lack of knowledge of the first symmetrybreaking steps in the Lophotrochozoa, even though the first described locus that reverses the whole body structure of an animal was from the pond snail Lymnaea [10, 11]
Commonalities between different species have been discovered [12,13,14,15]. In both vertebrates (Deuterostomia) and snails (Lophotrochozoa), nodal and pitx encode key signaling molecules required for the establishment of LR asymmetry, suggesting that these genes may have been used in the last common ancestor of Bilateria, but lost in Ecdysozoa [1, 2, 16]

Summary

Introduction

Given the importance of chiral patterning in the three bilaterian superphyla, Deuterostomia, Ecdysozoa, and Lophotrochozoa, a continuing problem is a lack of knowledge of the first symmetrybreaking steps in the Lophotrochozoa, even though the first described locus that reverses the whole body structure of an animal was from the pond snail Lymnaea [10, 11]. We use genetics, genomics, and pharmacological inhibition to show that the Lymnaea stagnalis chirality gene is a scaffolding component of the cytoskeleton.

Results

Conclusion