Labs Play Video Game Biology

For a gene that was almost named warthog and razorback and can claim a popular SEGA Genesis game as its name-sake, the Sonic hedgehog gene plays a crucial role in the development of animals.

Two Harvard research teams and one team from the Imperial Cancer Research Fund in Oxford, England, reported in the most recent issue of Cell that they have isolated Sonic hedgehog, a gene they believe is responsible for shaping the embryonic development of limbs and the central nervous system.

"Our research is very important for understanding certain aspects of limb development," said Clifford J. Tabin, assistant professor of genetics at the Medical School and the principal author of one the three papers that appeared in Cell describing the gene with the curious name.

Scientists have long known that the posterior, or bottom, portion of the limb bud is important in signalling for developmental patterning. The group's work "demonstrated that the Sonic hedgehog gene encodes the key substance that makes the bottom of the limb bud so special," Tabin said.

After the same gene was cloned in the fruit fly by other scientists, the three research groups became interested in searching for a similar gene present in vertebrate animals.

Apparently, cells sense the concentration of Sonic hedgehog and then decide what type of cells they should be--for example muscle, bone, or skin cells--and thus determine the ultimate shape of the embryo.

Professor of Biology and Biochemistry Andrew P. McMahon, the principal author of one of the three papers, found that the gene also works as a signal in parts of the central nervous system.

Scientists are excited that the isolation of the gene may have many implications for humans. "There is so much similarity in the limbs and we know so much about all of these systems that it's almost a certainty that this works the same way in humans," said Robert D. Riddle, a postdoctoral fellow working in Tabin's lab who isolated the new gene.

In fact, according to Tabin, in research subsequent to the publishing of the paper, his lab has isolated the human Sonic hedgehog gene. He has also mapped the genes responsible for certain genetically-determined diseases in humans to the same place on the chromosome as Sonic hedgehog.

One such disease is polydactyly, a disorder in which the affected individual suffers from an abnormal amount of fingers or toes.

Next, Riddle said, researchers must demonstrate that Sonic hedgehog is necessary as well as sufficient for limb development.

For the researchers, however, collaborating on their findings was far easier than deciding what to name the new gene. According to Tabin, each of the three labs had its own system of nomenclature, but only one name could be used in publication.

Tabin suggested using the names of different species of hedgehogs. His lab had called the previous three genes isolated from this family Indian hedgehog, moonrat hedgehog and desert hedgehog, for the gene's ability, when mutated, to give fruit flies the bristly appearance of a hedgehog.

But Riddle claimed that he didn't like any of the choices. According to Riddle, a co-author of one of the three papers, he went home and inadvertently picked up a copy of Games magazine, only to see an advertisement for Sonic Hedgehog 2, the SEGA Genesis video game.

"It seemed divinely inspired that I should call it that," he said.

However, the dispute did not end there. According to Tabin, Philip W. Ingham, a senior scientist at the Imperial Cancer Research Fund and the head of the third research team, did not like the name because in England Sonic is slang for "groovy" and "naming something Sonic made him sick." But he, too, eventually agreed to the name.

Daniel G. Jay, Loeb associate professor of the natural sciences, was enthusiastic about the teams' results. "I think their research is quite significant," said Jay, who studies neurodevelopment. "It's the first real clue as to the polarizing activity in the limb area and the nervous system."

While pleased with the results of the research, Tabin said that McMahon was not at all happy with the name. McMahon refused to comment on the issue, but did say that "we should not get hung up over a name."

But Tabin did have one concern. "Maybe I should wish that my post-docs were playing less computer games," he joked.