Long before anyone told you to drink milk to make your teeth strong, a complex system of genes made sure your molars ended up in the back of your mouth and your sharp incisors in front. In today's Science, researchers explain how they can force mouse tissue that should become an incisor to develop into a molar. The scientists hope the work, which helps them understand the signals that control tooth development, might eventually enable them to grow replacement teeth in humans who have lost a tooth to decay--or in a fist fight.
Developmental biologist Paul Sharpe of Guy's Hospital in London suspected that genes called Bmp-4 and Barx-1 were key to tooth shape. Previous work had shown, for example, that mice with a defective Barx-1 gene have no molars, and the BMP4 protein is present in the tissue above developing incisors--but not above molars. To see if these proteins control tooth shape, Sharpe and his colleagues Abigail Tucker and Karen Matthews rigged a way to grow teeth in isolation: They removed tissue from the developing jaw of a mouse embryo a few days after fertilization and placed it in the kidneys of adult mice. In about 2 weeks the transplanted tissue had sprouted adult teeth.
To find out what effect BMP4 might have, the team implanted a bead that released the protein into tissue that should have become a molar. In the region surrounding the bead, the Barx-1 gene--required for the development of molars--was dormant, evidence that BMP4 inhibits molar growth. To see what would happen to incisor tissue without BMP4, the team inserted a bead that released a protein called Noggin into developing incisor tissue. Noggin binds to BMP4 and prevents it from attaching to cells. The resulting tissue was full of Barx-1, and when it was allowed to grow in a host kidney, the incisor tissue became a molar.
The work is the first time anyone has been able to remake a developing tooth's identity by adding certain proteins, says developmental biologist Irma Thesleff of the University of Helsinki in Finland. But it will be years before dentists can put a "magic gel" into a patient's mouth to regenerate a tooth, Sharpe says: "You can't begin to think about that until you know what controls shape and size." Harold Slavkin, director of the National Institute of Dental and Craniofacial Research in Bethesda, Maryland, agrees. The work, he says, shows that molecular control over developing tissue is possible and allows scientists to "begin to think" of being able to design replacement parts.