Aging a gene that distinguishes left from right during development.

The left shell from Amphidromus preversus, an Indonesian snail, is sinistral (left-coiling) while the right one is dextral (right coiling).

The same gene that places a human's heart on the correct side of the body also controls whether a snail's shell twists left or right, scientists have found. The discovery suggests that this mechanism is far more ancient than researchers had thought.

All vertebrates express a gene called nodal on the left side of the embryo during early development. Nodal activates another gene, Pitx, leading to the body's normal asymmetry—some organs develop on one side, where there are high concentrations of nodal's protein product, while others develop where there are low levels. Though nodal is ubiquitous in vertebrates, researchers had been unable to find this gene in fruit flies (Drosophila) and the roundworm Caenorhabditis elegans, important model organisms.

These animals have left/right asymmetries but control them with a different system, says Nipam Patel, an HHMI investigator at the University of California, Berkeley. So, “the thought was that nodal hadn't been there in the common ancestor of flies, C. elegans, and people,” he says.

To see how other non-vertebrate organisms control asymmetry, Patel and Cristina Grande, a postdoctoral researcher in his lab, searched for nodal in a left-spiraling freshwater snail, commonly known as the bloodfluke planorb, and the owl limpet, a marine snail whose organs have the opposite orientation. Not only did they find nodal and Pitx, they also showed that, in concert with their asymmetries, the limpet expressed both these genes on the right side of the body, and the freshwater snail expressed both on the left.

The researchers went on to inhibit nodal signal in snails. “Most died,” says Patel, “but a fraction of those that survived had a straight shell.” The findings appeared February 19, 2009, in the journal Nature.

The study suggests that a common ancestor of snails and vertebrates used the nodal pathway to establish left-right asymmetry, explains Patel. The next step, he says, is to determine what activates nodal. Researchers partially understand the process in vertebrates, but “in snails classic genetic studies tell us that the mother puts something into the egg that initially establishes asymmetry, but we have no idea what this is.”

Photo: Patel lab