Notch Signaling Pathway in Tooth Shape Variations throughout Evolution
Thimios A. Mitsiadis,
Pierfrancesco Pagella,
Helder Gomes Rodrigues,
Alexander Tsouknidas,
Liza L. Ramenzoni,
Freddy Radtke,
Albert Mehl,
Laurent Viriot
Affiliations
Thimios A. Mitsiadis
Institute of Oral Biology, Center of Dental Medicine, University of Zurich, 8032 Zurich, Switzerland
Pierfrancesco Pagella
Institute of Oral Biology, Center of Dental Medicine, University of Zurich, 8032 Zurich, Switzerland
Helder Gomes Rodrigues
Centre de Recherche en Paléontologie-Paris (CR2P), UMR CNRS 7207, CP38, Muséum National d’Histoire Naturelle, Sorbonne Université, 75005 Paris, France
Alexander Tsouknidas
Laboratory for Biomaterials and Computational Mechanics, Department of Mechanical Engineering, University of Western Macedonia, 50100 Kozani, Greece
Liza L. Ramenzoni
Section of Computerized Restorative Dentistry, Center of Dental Medicine, University of Zurich, 8032 Zurich, Switzerland
Freddy Radtke
Ludwig Institute for Cancer Research, University of Lausanne, 1015 Lausanne, Switzerland
Albert Mehl
Section of Computerized Restorative Dentistry, Center of Dental Medicine, University of Zurich, 8032 Zurich, Switzerland
Laurent Viriot
Laboratoire de Biologie Tissulaire et d’Ingénierie Thérapeutique, Unité Mixte de Recherche 5305, Université Claude Bernard Lyon 1, CNRS, 69367 Lyon, France
Evolutionary changes in vertebrates are linked to genetic alterations that often affect tooth crown shape, which is a criterion of speciation events. The Notch pathway is highly conserved between species and controls morphogenetic processes in most developing organs, including teeth. Epithelial loss of the Notch-ligand Jagged1 in developing mouse molars affects the location, size and interconnections of their cusps that lead to minor tooth crown shape modifications convergent to those observed along Muridae evolution. RNA sequencing analysis revealed that these alterations are due to the modulation of more than 2000 genes and that Notch signaling is a hub for significant morphogenetic networks, such as Wnts and Fibroblast Growth Factors. The modeling of these tooth crown changes in mutant mice, via a three-dimensional metamorphosis approach, allowed prediction of how Jagged1-associated mutations in humans could affect the morphology of their teeth. These results shed new light on Notch/Jagged1-mediated signaling as one of the crucial components for dental variations in evolution.
