A Fish Story
A biologically elegant minnow is helping researchers decipher how we can grow our own replacement teeth.
Danio rerio is an unassuming fish, content to live out its life in the warm, sluggish tributaries of the Ganges River in East India and Burma. A small freshwater minnow, D. rerio never gets longer than three inches, and its distinctive horizontal blue stripes give the fish its common name, zebrafish.
A hardy, mellow species, zebrafish are popular low-maintenance aquarium fish. Beyond the fish bowl, they offer an elegantly simple model for scientists to study development and genetics. The females lay large numbers of transparent eggs that grow into adult fish in just two to four days. Since the 1970s, researchers have learned volumes about vertebrate development and the genes involved in the process by observing the humble little zebrafish.
"Zebrafish are a beautiful model system," said Pamela C. Yelick, G89, associate professor of oral and maxillofacial pathology at Tufts School of Dental Medicine. "You can do anything with them."
Though it serves as a terrific model, the zebrafish does have at least one feature not seen in many other vertebrates. It continuously sheds and regenerates its teeth over the course of its one-year life span. That's the biological trick Yelick and her team of researchers are trying to figure out. If they're successful, it could open a whole new array of treatment options for patients who lose their teeth.
On the eighth floor of the M&V building on Tufts' Boston campus, Yelick sprays her shoes and hands with disinfectant before opening the door to the room where 2,000 three-liter tanks currently hold 5,000 zebrafish. Eventually, her school of zebras will number 20,000 fish. She shows off the high-speed dishwasher for sanitizing lab tools, the incubators and brand new chemical hood that outfit her new lab space, and then frowns a bit at the leaky ceiling.
"We're still perfecting things. It's a new group, a refreshing environment," Yelick said of the research team she has assembled since she arrived at Tufts Dental School last fall. So far, she has two researchers—and zebrafish facility manager Caitlin Stewart Swift—dedicated to identifying the genes responsible for tooth regeneration in zebrafish. To do that, the researchers perform what is known in the biz as a "third-generation genetics screen" for craniofacial mineralized tissue defects in the families of zebrafish they've carefully bred and raised.
The scientists expose an adult male fish to a chemical that will induce a single base-pair mutation—essentially a one-letter typographical error in the DNA sentence—in each of his sperm cells. When these sperm fertilize unaltered, or wild-type eggs, the resulting fish each possess the same genetic typo. When this generation of fish is crossed with each other, some portion of them will possess the physical characteristic the DNA typo controls. By comparing these mutants' DNA to that of normal zebrafish, the Tufts researchers will discover which genes govern the tooth replacement process.
The team's goal is to devise gene therapies that will stimulate replacement tooth formation in people who have lost teeth due to disease or injury.
Yelick and Weibo Zhang, a researcher in the tissue engineering group.
"A lot of people are born without teeth or lose them due to periodontal disease," Yelick said. "It's very important to have healthy teeth, not only for esthetics, but for the systemic health of the entire body."
So Yelick is also working to grow replacement teeth in the lab. At the next bench over from the zebrafish team, the three-person tissue engineering group—Yan Lin, Ph.D., Weibo Zhang, D.M.D., Ph.D., and Wan-Peng Xu, D.M.D, Ph.D.—seeks to grow mammalian replacement teeth from postnatal dental stem cells.
"The two sides have a lot of interaction. They learn from one another. We have a unique combination of scientists here, which is a great advantage," Yelick said. "The old view of the scientist is of someone who works alone at a bench, but that person is not going to be a successful researcher." (continued)
Profile written by Jacqueline Mitchell
Photos by John Soares for Tufts University
This story ran online on Sept. 10, 2007. It originally appeared in the Summer 2007 edition of Tufts Dental Medicine.