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Form eines gesunden (links) und eines deformierten Mahlzahnes (Molar) mit deaktiviertem Jagged2-Gen (rechts) beim Maus-Embryo

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Shape of a healthy (left) and deformed molar with the Jagged2-gene deactivated (right) in the mouse embryo. (Image: UZH)

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Prof. Thimios Mitsiadis
Director of the Institute for Oral Biology at the Center for Dental and Oral Medicine and Cranio-Maxillofacial Surgery (ZZMK) University of Zurich


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News release, August 05, 2010

 

Gene brings teeth in shape

No healthy teeth without this gene: if during tooth formation (odontogenesis) the so-called Jagged2 gene is inactivated, and hence the Notch signaling pathway interrupted, tooth crowns will be malformed and enamel will be lacking. As this signaling pathway is involved in the formation of all tissues and organs, the new insights from the University of Zurich research team have wider implications.

Through the means of signaling pathways cells react to signals from their environment. One of the most important signaling pathways is the Notch signaling pathway. It is evolutionary conserved to a very high degree and it is involved in the development of all organs and tissues in animal and human embryos. The Notch signaling pathway enables neighboring cells to adopt different fates. By this mechanism signals exchanged via Notch receptors between neighboring cells control formation, development and differentiation of organs. Similarly, formation and differentiation of teeth is controlled by Notch signaling.

The research team of Thimios Mitsiadis, Professor for Oral Biology at the University of Zurich, has now shown that in mice the Jagged2 gene is required for the healthy development of teeth. Inactivation of this gene interrupts the Notch signaling pathway resulting in serious tooth malformations: The tooth crowns of the molars were deformed, additional cusps were formed. In incisors cell growth and enamel formation was blocked.

Bioteeth: one aim of stem-cell research

Understanding the Notch signaling pathway and knowing the genes that direct form and shape of tissues is important for many areas of biology. Within the field of dentistry these findings make an important contribution to our knowledge, particularly for the field of stem cell research, as Mitsiadis points out. Because there, the aim is to use the potential of stem cells not only for tooth repair, but ultimately for the generation of completely new teeth, called bioteeth. Therefore we require the knowledge of the precise genetic mechanisms that control tooth shape. To generate a new tooth whose shape suits a patient’s individual requirements is not possible today. A combined solution, however, is already thinkable with our current knowledge, Mitsiadis explains: «A combination of stem cells with an artificial scaffold could constitute a solution for this problem.»

Literature:

Thimios A. Mitsiadis, Daniel Graf , Hansueli Luder, Thomas Gridley, Gilles Bluteau: BMPs and FGFs target Notch signalling via jagged 2 to regulate tooth morphogenesis and cytodifferentiation, Development, Vol. 137 / Issue 18, 2010, doi:10.1242/dev.049528