Modeling Edar expression reveals the hidden dynamics of tooth signaling center patterning

When patterns are set during embryogenesis, it is expected that they are straightly established rather than subsequently modified. The patterning of the three mouse molars is, however, far from straight, likely as a result of mouse evolutionary history. The first-formed tooth signaling centers, call...

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Bibliographic Details
Published in:PLoS biology 2019-02, Vol.17 (2), p.e3000064
Main Authors: Sadier, Alexa, Twarogowska, Monika, Steklikova, Klara, Hayden, Luke, Lambert, Anne, Schneider, Pascal, Laudet, Vincent, Hovorakova, Maria, Calvez, Vincent, Pantalacci, Sophie
Format: Article
Language:English
Subjects:
Activation
Animals
Bernard, Claude (1813-1878)
Biochemistry, Molecular Biology
Biology and Life Sciences
Body Patterning
Chemotaxis
Development Biology
Developmental biology
Edar Receptor - genetics
Edar Receptor - metabolism
Embryogenesis
Embryology and Organogenesis
Embryonic growth stage
Epithelium - embryology
Epithelium - metabolism
Funding
Gene expression
Gene Expression Regulation, Developmental
Genomics
Hair
Hair - embryology
Insects
Life Sciences
Medicine and Health Sciences
Mice
Mice, Mutant Strains
Models, Biological
Molars
Morphogenesis
Pattern formation
Patterning
Premolars
Signal Transduction
Signaling
Supervision
Teeth
Tooth - embryology
Tooth - metabolism
Tooth Germ - embryology
Tooth Germ - metabolism
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Summary:When patterns are set during embryogenesis, it is expected that they are straightly established rather than subsequently modified. The patterning of the three mouse molars is, however, far from straight, likely as a result of mouse evolutionary history. The first-formed tooth signaling centers, called MS and R2, disappear before driving tooth formation and are thought to be vestiges of the premolars found in mouse ancestors. Moreover, the mature signaling center of the first molar (M1) is formed from the fusion of two signaling centers (R2 and early M1). Here, we report that broad activation of Edar expression precedes its spatial restriction to tooth signaling centers. This reveals a hidden two-step patterning process for tooth signaling centers, which was modeled with a single activator-inhibitor pair subject to reaction-diffusion (RD). The study of Edar expression also unveiled successive phases of signaling center formation, erasing, recovering, and fusion. Our model, in which R2 signaling center is not intrinsically defective but erased by the broad activation preceding M1 signaling center formation, predicted the surprising rescue of R2 in Edar mutant mice, where activation is reduced. The importance of this R2-M1 interaction was confirmed by ex vivo cultures showing that R2 is capable of forming a tooth. Finally, by introducing chemotaxis as a secondary process to RD, we recapitulated in silico different conditions in which R2 and M1 centers fuse or not. In conclusion, pattern formation in the mouse molar field relies on basic mechanisms whose dynamics produce embryonic patterns that are plastic objects rather than fixed end points.
ISSN:1545-7885
1544-9173
1545-7885
DOI:10.1371/journal.pbio.3000064