Trends in Genetics

Trends in Genetics

Volume 36, Issue 3, March 2020, Pages 189-202
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Review
Flipping Shells! Unwinding LR Asymmetry in Mirror-Image Molluscs

https://doi.org/10.1016/j.tig.2019.12.003Get rights and content

Highlights

  • Snails are the only animal group to ordinarily produce mirror-image forms. They have the potential to be an unequalled natural genetic resource in understanding chirality, including the invariant LR asymmetry of other animal groups.

  • A formin gene is associated with variation in LR asymmetry in two snail species, although the mutation is pathological in both. The genes that produce chiral variation without pathology are still wholly unknown; changes in gene expression or of accessory factors are likely.

  • Understanding LR asymmetry in snails will involve studies of early embryology and genomics, alongside whole-animal studies on the impact of natural and sexual selection.

  • Chiral variation in snails may be enabled by the dichotomous nature of spiralian cleavage (dextral or sinistral), combined with the action of selection on the outward shell phenotype.

In seeking to understand the establishment of left–right (LR) asymmetry, a limiting factor is that most animals are ordinarily invariant in their asymmetry, except when manipulated or mutated. It is therefore surprising that the wider scientific field does not appear to fully appreciate the remarkable fact that normal development in molluscs, especially snails, can flip between two chiral types without pathology. Here, I describe recent progress in understanding the evolution, development, and genetics of chiral variation in snails, and place it in context with other animals. I argue that the natural variation of snails is a crucial resource towards understanding the invariance in other animal groups and, ultimately, will be key in revealing the common factors that define cellular and organismal LR asymmetry.

Section snippets

The Establishment of LR Asymmetry

While most animal bodies are bilaterally symmetric on the outside, the internal organs usually show a consistent LR asymmetry (see Glossary). Defining this LR asymmetry is a critical part of early development, such that left/right positional errors are an important class of human birth defects and, in later life, numerous diseases affect apparently symmetric organs in an asymmetric fashion [2., 3., 4.]. Yet, while a wealth of studies have been important in revealing the genes that promote the

A Twisted History of Embryology and Genetics in Snails

It has long been known that the direction of the chiral twist that takes place during the third cleavage corresponds to the shell coiling direction and body asymmetry of the adult snail [22]. During the early days of Mendelian genetics, Boycott and Diver [23] reported that shell coiling in the pond snail Lymnaea (Radix) peregra was a hereditary character, although the pattern of inheritance was difficult to understand. Sturtevant [24] responded and suggested that chirality is an exceptionally

Unwinding Snail Chirality

In an initially surprising finding (Box 2), it was discovered that at least two genes, including the TGF-β gene nodal, are involved in LR signalling in both vertebrate (Deuterostomia) and molluscan (Lophotrochozoa) asymmetry, yet are absent in derived animals, such as nematodes and fruit flies (Ecdysozoa) [5]. Then, it was shown that asymmetry in snails has much in common with other taxa that lack nodal. Thus, while the unequivocally first symmetry-breaking event in nematodes and snails is

Defining LR Asymmetry in the Cytoskeleton

Until recently, the means by which interacting sets of actin assembly factors work together in cells had remained obscure. This is unfortunate because a basic understanding of actin dynamics is a prerequisite for understanding how molecular chirality defines cellular chirality in snails.

One point of progress has been in understanding how cellular chirality arises from the self-organisation of the actin cytoskeleton (reviewed in [14,46]), and biomechanical forces in general [15]. By studying

From Chiral Cells to Chiral Shells

How is chirality transmitted from molecules to cells? Studies in the nematode have shown that the clockwise tilt of two blastomeres at the four–six cell-stage transition, which marks the initiation of LR asymmetry, is matched by counter-rotating chiral cortical flows along the divisional axes. Changing the flow speed changes the degree of blastomere rotation, indicating that intracellular chiral flow is directing symmetry breaking [63]. More generally, there is an increasing focus on LR

How Do Snails Commonly Vary in Their LR Asymmetry?

I began by highlighting the irony that molluscs, mainly snails, are the only animal group to vary in their LR asymmetry, yet many scientists are welded to studying invariant model species, mostly vertebrates, flies, or nematodes. More specifically, the invariant LR asymmetry of other spiralian phyla is rarely considered against the varying LR asymmetry of snails, despite fundamental similarities in their development [75]. There is an apparent paradox. Sinistral species of snails have evolved

Flipping Shells

A hypothesis is that snails vary in their chirality because of the combined effect of natural selection on the outward phenotype and the dichotomous switch of spiral cleavage during early development (Figure 3). Thus, while a body of research shows that the LR asymmetry is coded in the single-cell embryo, the twist of the third cleavage is the key moment that defines morphological body asymmetry. It is a dichotomous chiral switch that cannot be supressed by other pathways or redundancies [32,85

Concluding Remarks and Future Perspectives

Unlike any other animal group, snails commonly vary in their LR asymmetry. Although recent progress has implicated the cytoskeleton as key, the set of genes that determine chiral change are not known, nor how this is possible without pathology (see Outstanding Questions). I argue that constraints to chiral change are likely the default in all animals, except in snails, where new chiral variants can sometimes be favoured. This may be enabled by the dichotomous nature of spiralian cleavage and

Acknowledgements

I would like to thank Cristina Grande, Michael Levin, Menno Schilthuizen, Sundar Naganathan, Stéphane Noselli, Naoki Watanabe, and two anonymous referees for enjoyable discussions, and comments on the manuscript, and to Ken Hayes and Norine Yeung, for enabling field work.

Glossary

Chiral
an object that is asymmetric in such a way such that it is nonsuperimposable on its mirror image. A cell may have radial symmetry, by gross morphology, but contain a chiral cytoskeleton. A snail shell has LR asymmetry and is also chiral.
Cytoskeleton
the scaffolding of a cell, involving a network of protein filaments and microtubules in the cytoplasm that control cell shape, maintain intracellular organisation, and are involved in cell movement.
Dextral or sinistral
in this context, whether

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