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Notch Signaling Pathway in Tooth Shape Variations throughout Evolution
Thimios A Mitsiadis1, Pierfrancesco Pagella1, Helder Gomes Rodrigues2
1Institute of Oral Biology, Center of Dental Medicine, University of Zurich, 8032 Zurich, Switzerland.
Cells
|March 11, 2023
Summary
Genetic alterations in tooth crown shape influence vertebrate evolution. Loss of Jagged1 in mice modifies tooth cusps, revealing Notch signaling
Area of Science:
- Developmental Biology
- Evolutionary Biology
- Genetics
Background:
- Vertebrate evolutionary changes are linked to genetic alterations affecting tooth crown shape, a key speciation criterion.
- The conserved Notch pathway regulates morphogenetic processes in developing organs, including teeth.
Purpose of the Study:
- To investigate the role of the Notch-ligand Jagged1 in tooth crown development and evolution.
- To understand how Jagged1-associated mutations may impact human dental morphology.
Main Methods:
- Epithelial Jagged1 loss in developing mouse molars.
- RNA sequencing to analyze gene expression changes.
- Three-dimensional metamorphosis modeling of tooth crown alterations.
Main Results:
- Loss of Jagged1 resulted in modified cusp location, size, and interconnections, causing minor tooth crown shape changes.
- These modifications were convergent with observed changes in Muridae evolution.
- Notch signaling modulates over 2000 genes and acts as a hub for morphogenetic networks like Wnts and FGFs.
Conclusions:
- Notch/Jagged1 signaling is a crucial component of dental variation during evolution.
- Modeling tooth crown changes in mice predicts potential effects of Jagged1 mutations in humans.
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