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Notch Signaling Pathway in Tooth Shape Variations throughout Evolution


Mitsiadis, Thimios A; Pagella, Pierfrancesco; Gomes Rodrigues, Helder; Tsouknidas, Alexander; Ramenzoni, Liza L; Radtke, Freddy; Mehl, Albert; Viriot, Laurent (2023). Notch Signaling Pathway in Tooth Shape Variations throughout Evolution. Cells, 12(5):761.

Abstract

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.

Abstract

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.

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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > Center for Dental Medicine > Clinic of Conservative and Preventive Dentistry
04 Faculty of Medicine > Center for Dental Medicine > Institute of Oral Biology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > General Biochemistry, Genetics and Molecular Biology
Uncontrolled Keywords:Jagged1; RNA analysis; dental morphology; differentiation; evolution; human; mouse; notch signaling; tooth
Language:English
Date:27 February 2023
Deposited On:06 Nov 2023 13:54
Last Modified:29 Apr 2024 01:40
Publisher:MDPI Publishing
ISSN:2073-4409
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.3390/cells12050761
PubMed ID:36899896
  • Content: Published Version
  • Language: English
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)