As soon as the story was out last winter, Chrissa Kioussi’s phone started to ring. More than 50 callers from Europe, South America, Australia and the United States offered to send her their teeth or even to come to Corvallis to volunteer in her study of tooth development.
Though grateful for their interest, Kioussi turned them all down. “It was unbelievable,” she says. “I was not prepared for something like that.”
The calls followed the news that, in trials with laboratory mice, a team of scientists at Oregon State University and a French research institute (Institut de Génétique et de Biologie Moléculaire et Cellulaire) had found one of the keys to building healthy teeth. They reported in the Proceedings of the National Academy of Sciences (PNAS) that a gene called Ctip2 acts as a kind of conductor, directing tooth-building cells to make enamel at the right place and time.
Nicknamed the “tooth fairy gene” by Discover magazine, Ctip2 could eventually help researchers grow natural teeth and replace those damaged by injury, disease or poor diet. The PNAS report was the first to pinpoint the importance of Ctip2, known as a transcription factor, for developing teeth. “This is the first transcription factor ever found to control the formation and maturation of ameloblasts, which are the cells that secrete enamel,” says Kioussi.
Matter of Survival
A developmental biologist in the OSU College of Pharmacy, Kioussi calls the discovery an accident.
She and her colleagues — including post-doctoral scientist Olga Golonzhka and faculty members Mark Leid, Michael Gross and Brian Bay at OSU — were studying mice that lack Ctip2 altogether or have only one copy. Two copies are needed for healthy development, and the researchers observed that about 30 percent of mice with one copy, she says, had malformed incisors that would have been too soft for chewing. Mice are omnivores, but nuts and grains are common in their diet. “They would not have survived,” Kioussi adds.
The question was, How did these proto-teeth get that way? As early as the 10th day after a mouse embryo begins to develop, Kioussi and her colleagues reported, Ctip2 is active in the tissues that will become jaw and teeth. Without this gene, which also regulates development of nerves, skin and immune cells, the process goes badly awry.
From Cell to Tooth
OSU scientists are well prepared to investigate this genetic maestro. During a sabbatical in France in 2001, Leid developed a unique strain of mice that does not have the Ctip2 gene. Now, with financial support from the National Institutes of Health and College of Pharmacy, the OSU researchers have established a mouse genetics facility that is yielding insights into human health.
The tooth discovery could have far-reaching benefits. A British company that makes tooth implants, says Leid, has shown interest in replacing them with natural teeth, possibly developed from adult stem cells. And because enamel is one of the hardest biological compounds in nature, engineers are experimenting with its use in industrial design. Kioussi is now working with dental researchers at the University of Southern California to examine the entire development process from adult stem cell to mature tooth.
For more about Kioussi’s research, see this OSU news relase
Genetic Discovery Could Lead to Advances in Dental Treatment, February 23, 2009
And this story from the British Broadcasting Corporation (BBC)
To support research in the OSU College of Pharmacy, contact the Oregon State University Foundation.