Researchers identify key gene network responsible for severe tooth enamel defects

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Mutations in a certain molecule lead to severe damage in the structure and mineral composition of tooth enamel in mice, according to a study conducted at the UZH Center for Dentistry. The researchers combined genetic, molecular and imaging techniques.

Enamel is the hardest organic tissue found in nature. It has a very complex structure, made up of enamel-specific minerals and proteins produced by teeth-exclusive cells called ameloblasts. However, no matter how strong tooth enamel is, it is still susceptible to damage: enamel defects are among the most common dental problems and lead, among other things, to pain-sensitive teeth and an increased risk of cavities.

Zoom on the Adam10 molecule

A team of researchers from the Center for Dentistry at the University of Zurich has just identified for the first time a network of key genes responsible for serious defects in tooth enamel. Using various genetically modified mouse models, the scientists analyzed the effects of the Adam10 molecule, which is closely linked to the Notch signaling pathway. This signaling pathway allows communication between adjacent cells, is essential for embryonic development and plays a crucial role in the development of severe human pathologies such as strokes and cancer. To investigate in detail the role of Adam10/Notch signaling in the formation and pathology of tooth enamel and to analyze changes in cellular structure and tooth enamel upon gene mutation, the researchers used state-of-the-art genetic, molecular and imaging tools. .

Defects in enamel structure and mineral composition

Scientists were able to demonstrate that there is a close link between impaired Adam10/Notch function and enamel defects.

Mice with Adam10 mutations have teeth with severe enamel defects. Deletion of Adam10 causes disorganization of ameloblasts, which then leads to severe defects in both structure and mineral composition of enamel.”


Thimios Mitsiadis, Professor of Oral Biology, Center for Dentistry and Study Leader

Adam10-dependent Notch signaling is therefore not only implicated in severe pathological conditions, but also in the organization and structure of developing tissues, such as teeth.

New avenues for prevention and therapy

According to Mitsiadis, understanding the genetic code that controls the development of teeth, knowing the molecular connections during the formation of enamel and the impact of mutations leading to enamel malformations open up new horizons in the field of prevention and treatment. “The requirements for enamel repair and de novo formation are extremely complex, but new genetic and pharmaceutical tools targeting impaired tooth enamel formation will allow us to dramatically improve dental care in the future.”

Source:

Journal reference:

Mitsiadis, TA, et al. (2022) Adam10-dependent Notch signaling establishes dental epithelial cell boundaries necessary for enamel formation. iScience. doi.org/10.1016/j.isci.2022.105154.

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