But that can’t be the whole story because by the time the cilia start to beat, the embryo is already asymmetrical. There must be some earlier symmetry-breaking event.
To find it, Angus Davison from the University of Nottingham turned to pond snails, some of the most obviously asymmetrical animals around. Their shells spiral in either a right-handed clockwise direction or a left-handed anticlockwise one—an obvious outward difference that reflects subtler internal ones.
In 2010, Reiko Kuroda showed that these asymmetries begin in the snail’s earliest moments. Like all of us, they begin life as a single cell, which divides into two, and then into four. At this stage, all the cells are the same size and shape. But the next division is unequal, pinching off a small cell on top of a big one—picture four ping pong balls sitting on top of four tennis balls. The ping pong-sized cells then rotate to nestle between the furrows of the tennis-sized ones. If they rotate clockwise, the snails end up with a right-handed shell. When Kuroda nudged them anticlockwise, using glass rods and exceptional dexterity, she produced left-handed shells.
But what makes the smaller cells do the twist in the first place? Back in the 1920s, scientists showed that handedness is pond snails is heritable. Individuals inherit a gene from their mothers that defines the direction of their twist, and the version that causes clockwise rotations is dominant. But which gene?
Davison found it by teaming up with geneticist Mark Blaxter at the University of Edinburgh. After several years of work, they eventually homed in on a gene called Ldia2, which produces a protein called formin. To their astonishment, the team found that even when snail embryos consist of just two cells, they’re already asymmetrical—one of the cells contains more formin than the other. And by the four-cell stage, formin is largely confined to just one cell.
Formin interacts with a cell’s cytoskeleton, a mesh of long, wiry proteins that give it shape and structure. Davison and Blaxter think that formin interacts with the cytoskeleton in an asymmetric way, which puts a twist on the cell’s shape, and triggers the early rotations.
The team supported this idea by dousing snail embryos with a chemical that stops formin from interacting with the cytoskeleton. In doing so, they changed genetically right-handed snails into left-handed ones. And they found that naturally left-handed snails inherit a version of Ldia2 that’s missing a single DNA letter, and produces a stunted, broken version of formin. The cells destroy the faulty protein, so no rotations occur, and the snails grow up left-handed.
“But we don’t really know,” stresses Blaxter. They have the gene, and they know how it differs in right-handed and left-handed snails, but they still need to confirm how it works. “That’ll take another four years of careful cell biology.”