Researchers Study Fish to Regenerate Teeth

Photo by Rob Felt, Georgia Tech.

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Photo by Rob Felt, Georgia Tech.

When a fish loses a tooth, a new one grows in. But human beings only get 2 sets of teeth in their lifetime. Now, scientists at the Georgia Institute of Technology and King’s College in London are looking to our finny friends to see how we can grow our teeth back, too.

The researchers are studying how the structures in embryonic Lake Malawi cichlids differentiate into teeth or taste buds so they can activate a similar tooth regeneration mechanism in people. The work also involved dental differentiation in mice, showing that the structures responsible for growing new teeth may remain active longer than previously thought.

“We have uncovered developmental plasticity between teeth and taste buds, and we are trying to understand the pathways that mediate the fate of cells toward either dental or sensory development,” said Todd Streelman, a professor at the Georgia Tech school of biology.

Streelman worked with Ryan Bloomquist, a DMD/PhD student at Georgia Tech and Georgia Regents University, to study how teeth and taste buds grow from the same epithelial tissues in embryonic fish. Since fish have no tongues, their taste buds are mixed in with their teeth, sometimes in adjacent rows.

One species of the Lake Malawi cichlids eats plankton and needs few teeth because it locates its food visually and swallows it whole. Another species lives on algae, which must be scraped or snipped from rocky lake formations, requiring many more teeth and taste buds.

The researchers crossed the species and saw substantial variation in the numbers of teeth and taste buds in the second generation of hybrids. By studying the genetic differences in some 300 of these hybrids, the researchers discovered the genetic components of the variation.

“We were able to map the regions of the genome that control a positive correlation between the densities of each of these structures,” said Streelman. “And through a collaboration with colleagues at King’s College in London, we were able to demonstrate that a few poorly studied genes were also involved in the development of teeth and taste buds in mice.”

By bathing embryonic fish in chemicals that influence the pathways involved in tooth and taste bud formation, the researchers manipulated the development of the 2 structures. In one case, they boosted the growth of taste buds at the expense of teeth. These changes were initiated just 5 or 6 days after the eggs were fertilized, when the fish had eyes and a brain but were still developing jaws.

“There appear to be developmental switches that will shift the fate of the common epithelial cells to either dental or sensory structures,” said Streelman.

Teeth and taste buds originate in the same kind of epithelial tissue in the developing jaws of embryonic fish, differentiating later, either forming teeth with hard enamel or soft taste buds. With the right signals, human epithelial tissue also might be able to regenerate new teeth.

“It was not previously thought that development would be so plastic for structures that are so different in adult fish,” said Streelman. “Ultimately, this suggests that the epithelium in a human’s mouth might be more plastic than we had previously thought.”

But growing new teeth isn’t enough, Streelman said. Researchers also must understand how nerves and blood vessels grow into teeth to make them viable. Streelman next will work with research technician Teresa Fowler to determine how far into adulthood the plasticity between teeth and taste buds extends, as well as what can trigger the change.

The study, “Co-Evolutionary Patterning of Teeth and Taste Buds,” was published by the Proceedings of the National Academy of Sciences and supported by the National Institute of Dental and Craniofacial Research. Researchers also included professor Paul Sharpe and Tian Yu of King’s College and Nicholas Parnell and Kristine Phillips of Georgia Tech.

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