Scientists Study Differences in Mammalian Teeth Versus Shark Teeth

Dentistry Today

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Mammals develop a single row of teeth, while sharks have several rows of teeth. A study published in the journal Science describes a genetic program that may help guide efforts to regrow missing teeth and prevent cleft palate. Researchers discovered that turning off a single gene in mice resulted in development of extra teeth. While the study was in mice, past studies have shown that the involved biochemical players are active in humans as well. 

“It takes the concerted actions of hundreds of genes to build a tooth, so it was amazing to find that deleting one gene caused the activation of a complete tooth developmental program outside of the normal tooth row in those mice. Finding out how the extra teeth developed will reveal how nature makes a tooth from scratch, which will guide tooth regeneration research,” said Rulang Jiang, PhD, associate professor of biomedical genetics in the Center for Oral Biology at the University of Rochester Medical Center. 

Jiang, et al generated mice that lacked the odd-skipped related-2 (Osr2) gene, which encodes one of many transcription factors that turn genes on or off. Deleting the Osr2 gene re-sulted in cleft palate, and these mice also developed teeth outside of the normal tooth row. Bone morphogenic protein 4 (BMP4) is an important factor for the initiation of teeth, and a protein called Msh homeobox 1 (Msx1) amplifies the BMP4 tooth-generating signal. They suggested for the first time that some unknown factor was restricting the growth of teeth into one row by opposing the BMP4 signal. The current study provides the first solid proof that the precise space where mammals can develop teeth (the “tooth morphogenetic field”) is shaped and restricted by the effect of Osr2 on the expression of the BMP4 gene within the mesenchymal cell layer. Dr. Jiang’s team has shown not only that removing the Osr2 gene results in extra teeth outside of the normal row, but also that Osr2 is expressed in increasing concentration in the jaw mesenchyme moving from the cheek toward the tongue in the mouse embryo, the exact opposite of the BMP4 concentration gradient. Osr2 restricts BMP4 expression to the tooth mesenchyme under the dental lamina, and in Osr2’s ab-sence, BMP4 gene expression expands into the jaw mesenchyme outside of the tooth row. The implications of the current results may go beyond tooth development, said the researchers. Thanks to the work of Dr. Jiang’s team, some of the biochemical pathways involved in cleft lip/cleft palate development are now recognized, and may include BMP4, Msx1, and Osr2 as well as several others. In humans, Msx1 mutations have been linked with cleft lip/palate and with the failure to develop one or more teeth. In the next phase of the team’s work, re-searchers will look at what other factors may be regulated by Msx1 and Osr2 to begin pinpointing the genetic network that controls teeth patterning and palate development. Their goal is to manipulate stem cells to treat malformations and to develop prevention strategies for cleft palate. 


(Source: ScienceDaily.com, February 27, 2009. Clinical Reference: Jiang R, et al. Antagonistic actions of Msx1 and Osr2 pattern mammalian teeth into a single row. Science. 2009;323(5918): 1232-1234)