Handedness — asymmetrical anatomy or behaviour — is a fundamental feature of many animals, but how it occurs remains a mystery. Snails can also show ‘handedness’ — some individuals have shells that spiral in a right-handed direction, others have left-handed shells. Scientists call this twisted form of handedness ‘chirality’. Differences in shell twist can help produce new species, as individuals of opposite chirality cannot mate.
The genetic basis of this variability can be remarkably simple — in Lymnaea stagnalis chirality is determined by a single gene or a small set of genes that is inherited from the mother, with the right-hand twist form of the gene being dominant. However, neither the gene involved nor its developmental pathways are known.
In an astonishing piece of experimental dexterity, a group of Japanese scientists, led by chirality chemist Reiko Kuroda, have used a combination of genetics and physical manipulation to reveal exactly how the snail shell gets its twist.
In its first stages, the snail embryo shows no sign of chirality; however, after the embryo's third cleavage, when it grows from four to eight cells, information about the future shell twist is present. Kuroda and her colleagues demonstrated this by literally poking about in the embryo.
They used minute glass rods to push around cells in the eight-cell embryo, making the cells establish new connections typical of embryos with the opposite twist to that expected from the embryo's genes. In over 75% of cases, they were able to successfully ‘re-programme’ snail embryos, from right-handed to left-handed twist, and vice versa. If they carried out the same experiment at an earlier stage, when there were only two cells, it had no effect.
To see whether successfully manipulated embryos would produce re-twisted snails, they reared the embryos to adulthood and studied their external and internal anatomy. In every case, the snails were fully reversed in every respect compared with the handedness expected from their genes.
The key developmental change, which takes place as the embryo grows from four to eight cells, involves the twist-determining gene, which affects the way the protein Nodal is expressed, leading to handedness in the way the snail is organized.
Exactly how this happens and above all how cells ‘remember’ exactly which way they are supposed to be twisting remain unknown. The delicate micromanipulation at the heart of this elegant study provides a vital tool for investigating the origins and nature of handedness, not only in spiral organisms like snails but also in other animals.