Veteran exterminators and terrified homeowners tell horror stories of rodents gnawing their way through wood, plaster, even lead pipes. Now, scientists have uncovered the molecular mechanism responsible for maintaining the ultrasharp teeth of mice. The findings help explain the unusual development of the enamel coating on rodent incisors.
Incisors are the cutting teeth located at the front of the mouth. In rodents, these teeth grow continuously to avoid being worn down. But what really keeps them sharp is the fact that they are only covered by enamel on the outside of the tooth closest to the lips. This creates a ridge of hard enamel that acts like a knife. In most mammals, including humans, the enamel covers all of the exposed tooth. Scientists have long been puzzled as to what mechanism accounts for the dramatic asymmetry in enamel growth.
Developmental biologist Irma Thesleff of the University of Helsinki, Finland, had a hunch that a protein called follistatin, already known to play an important role in embryonic development, might hold a key to the mystery. Thesleff and her team used genetically engineered mice to test their hypothesis. Mice missing the gene for follistatin produced enamel on both sides of their incisors, whereas the enamel layer was completely absent in mice engineered to overproduce the protein. The researchers also showed that follistatin was expressed at much higher levels in the enamel-free side of the teeth of normal mice. These findings showed that follistatin keeps teeth sharp by blocking enamel formation on one side.
Additional studies determined that follistatin works by inhibiting a family of signaling molecules--known as bone morphogenetic proteins--responsible for stimulating the development of enamel-producing cells, the team reports in the November issue of Developmental Cell.
Similar inhibitory mechanisms may also be important in how the enamel-free roots of human teeth are formed, says Salomon Amar, a molecular and cell biologist at Boston University. He says the new work is an "important contribution" to both our understanding of developmental biology and the formation of teeth in general.