Story posted October 04, 2010
Where do teeth come from? It’s a question Assistant Professor of Biology Bill Jackman has been asking for most of his career. It's also one that has become quite personal for one of his student researchers, Pawat Seritrakul ’11, who has been working in Jackman’s lab for two years.
Early on in their study of tooth development and evolution in zebrafish, Seritrakul suddenly realized he had an extra molar on his upper right side, 33 teeth in all. Not only that, genetic experiments he conducted during his first summer identified a molecule that signaled the embryonic fish's cells to make extra teeth.
"I feel sort of special that I have an extra tooth, which might have arisen from the same mechanism I am studying in the lab right now," he says. "Working on this not only answers a fundamental biological question but also my very own question about how my mother gave me an extra tooth."
Zebrafish are an ideal model organism for studying tooth development, partly because they produce so many offspring. The popular freshwater aquarium fish reach sexual maturity at three to four months of age and then can breed every morning, producing approximately 500 embryos per day.
The fish develop quickly; the earliest signs of teeth are visible just a few days after fertilization and erupt in early stages of development. Their teeth that form are pharyngeal—located in their throats—instead of oral, an adaptation that occurred millions of years ago.
To try to identify the genes involved in tooth formation, Seritrakul added retinoic acid, a metabolite of vitamin A, to the developing fish. The resulting zebrafish had extra teeth and ectopic teeth (teeth outside the pharynx), indicating that retinoic acid plays a key role in tooth development.
"There are a lot of genes that are required to make a normal tooth, but not all proteins or gene products are capable of telling cells to develop teeth," says Jackman. "We knew that retinoic acid was involved in tooth formation, but there was no evidence about it being sufficient to cause cells to form extra teeth."
The significance of retinoic acid is just one piece of the puzzle. Jackman and his student researchers also are examining dlx2b, a gene that is expressed in zebrafish tooth germs very early, but not in surrounding tissue. This pattern suggests that dlx2b is involved in the early development of teeth, but it’s not the initiating molecular signal.
To find that molecular signal, Jackman and his students are examining genomic regulatory sequences located near dlx2b. These sequences can potentially lead them to the genes that initiate tooth formation during development.
Ultimately, their research on tooth development in embryonic zebrafish may add to significant advances in human dentistry.
"The issue of tooth replacement or regeneration is a big one," notes Jackman. "Already, we naturally replace our milk teeth with permanent teeth. But fish replace teeth their entire lives. If we can understand what genes do in embryonic development we may be able to coax them on a case-by-case basis to re-grow another tooth, rather than having dentures or even a root canal."
“I am really drawn into this field of developmental/evolutionary biology,” says Seritrakul. “Watching a zebrafish embryo developing from a single cell into an adult fish is almost like watching a clump of metal turning into a Boeing 747.”
Jackman's research is supported by a grant from Maine's IDeA Networks of Biomedical Research Excellence (INBRE).