«Subjects afflicted by DiGeorge syndrome exhibit teeth with enamel defects. We have demonstrated that a direct link between impaired Tbx1 function and enamel defects exists. Enamel forms via the mineralization of specific enamel proteins that are secreted by dental epithelial cells called ameloblasts. Our results clearly show that teeth of Tbx1 null mice lacked enamel and ameloblasts» explains Prof Mitsiadis.
These findings, just published in Development Biology, represent a major contribution to the understanding of the production of enamel, the «hardest organic tissue» found in nature.
An American group of researchers from the University of Oregon have also shown a relationship between another transcription factor (Ctip2) and the production of enamel, but in the words of Prof Mitsiadis «our investigations better demonstrate the lack of enamel in teeth. Because of the early lethality of the Tbx1 mutant mice, we have used long-term culture techniques that allow the unharmed growth of teeth until their full maturity. No such studies were performed from our American colleagues». Could dental treatment benefit in the future from this revolutionary study? The answer is definitively yes. «The understanding of the genetic code controlling tooth development and repair will permit us to imagine and generate new products and replacement tissues for injured and unhealthy teeth. However the requirements for functional tooth repair and/or formation are complex. Yet, a single approach has not allowed an effective clinical therapy» says Prof Mitsiadis.
Is it possible to use dental stem cells to stimulate the growth of new enamel? This represents the biggest challenge in the discipline of tooth engineering. «Our results show that Tbx1 is involved in the maintenance of dental epithelial stem cells that are responsible for ameloblast formation. In some cases of genetic tooth anomalies, regeneration and repair of teeth could be treated by stem cells. Aggregates of dental stem cells could be used in the future for local transplantation in the dental tissues» explains Prof Mitsiadis.
For more than twenty years Professor Mitsiadis has been studying the molecular basis and interactions involved in tooth development, pathology and regeneration. A major milestone in his previous research was the creation of teeth in chick embryos after transplantation of mouse neural crest cells (http://www.pnas.org/content/100/11/6541.full). He is the director of the Institute of Oral Biology at the University of Zurich since 2006. His work is now focusing in the identification of genes involved in dental pathology and regeneration and on the regulatory mechanisms that control stem cell development.
Catón, Javier, Luder, Hans-Ulrich, Zoupa, Maria, Bradman, Matthew, Bluteau, Gilles, Tucker, Abigail S., Klein, Ophir, Mitsiadis, Thimios A.: Enamel-free teeth: Tbx1 deletion affects amelogenesis in rodent incisors, in: Developmental Biology (2009), doi:10.1016/j.ydbio.2009.02.014.