Wnt/β-Catenin Regulates the Activity of Epiprofin/Sp6, SHH, FGF, and BMP to Coordinate the Stages of Odontogenesis.
- Aurrekoetxea M Department of Cell Biology and Histology, Faculty of Medicine and Dentistry, University of the Basque Country UPV/EHU Leioa, Spain.
- Irastorza I Department of Cell Biology and Histology, Faculty of Medicine and Dentistry, University of the Basque Country UPV/EHU Leioa, Spain.
- García-Gallastegui P Department of Cell Biology and Histology, Faculty of Medicine and Dentistry, University of the Basque Country UPV/EHU Leioa, Spain.
- Jiménez-Rojo L Center of Dental Medicine, Institute of Oral Biology, University of Zurich Zurich, Switzerland.
- Nakamura T Division of Molecular Pharmacology and Cell Biophysics, Department of Oral Biology, Graduate School of Dentistry, Tohoku University Sendai, Japan.
- Yamada Y Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health Bethesda, MD, USA.
- Ibarretxe G Department of Cell Biology and Histology, Faculty of Medicine and Dentistry, University of the Basque Country UPV/EHU Leioa, Spain.
- Unda FJ Department of Cell Biology and Histology, Faculty of Medicine and Dentistry, University of the Basque Country UPV/EHU Leioa, Spain.
- 2016-04-12
Published in:
- Frontiers in cell and developmental biology. - 2016
English
BACKGROUND
We used an in vitro tooth development model to investigate the effects of overactivation of the Wnt/β-catenin pathway during odontogenesis by bromoindirubin oxime reagent (BIO), a specific inhibitor of GSK-3 activity.
RESULTS
Overactivating the Wnt/β-catenin pathway at tooth initiation upregulated and ectopically expressed the epithelial markers Sonic Hedgehog (Shh), Epiprofin (Epfn), and Fibroblast growth factor8 (Fgf8), which are involved in the delimitation of odontogenic fields in the oral ectoderm. This result indicated an ectopic extension of the odontogenic potential. During tooth morphogenesis, Fibroblast growth factor4 (Fgf4), Fibroblast growth factor10 (Fgf10), Muscle segment homeobox 1 (Msx-1), Bone Morphogenetic protein 4 (Bmp4), and Dickkopf WNT signaling pathway inhibitor 1 (Dkk-1) were overexpressed in first molars cultured with BIO. Conversely, the expression levels of Wingless integration site 10b (Wnt-10b) and Shh were reduced. Additionally, the odontoblast differentiation markers Nestin and Epfn showed ectopic overexpression in the dental mesenchyme of BIO-treated molars. Moreover, alkaline phosphatase activity increased in the dental mesenchyme, again suggesting aberrant, ectopic mesenchymal cell differentiation. Finally, Bmp4 downregulated Epfn expression during dental morphogenesis.
CONCLUSIONS
We suggest the presence of a positive feedback loop wherein Epfn and β-catenin activate each other. The balance of the expression of these two molecules is essential for proper tooth development. We propose a possible link between Wnt, Bmp, and Epfn that would critically determine the correct patterning of dental cusps and the differentiation of odontoblasts and ameloblasts.
We used an in vitro tooth development model to investigate the effects of overactivation of the Wnt/β-catenin pathway during odontogenesis by bromoindirubin oxime reagent (BIO), a specific inhibitor of GSK-3 activity.
RESULTS
Overactivating the Wnt/β-catenin pathway at tooth initiation upregulated and ectopically expressed the epithelial markers Sonic Hedgehog (Shh), Epiprofin (Epfn), and Fibroblast growth factor8 (Fgf8), which are involved in the delimitation of odontogenic fields in the oral ectoderm. This result indicated an ectopic extension of the odontogenic potential. During tooth morphogenesis, Fibroblast growth factor4 (Fgf4), Fibroblast growth factor10 (Fgf10), Muscle segment homeobox 1 (Msx-1), Bone Morphogenetic protein 4 (Bmp4), and Dickkopf WNT signaling pathway inhibitor 1 (Dkk-1) were overexpressed in first molars cultured with BIO. Conversely, the expression levels of Wingless integration site 10b (Wnt-10b) and Shh were reduced. Additionally, the odontoblast differentiation markers Nestin and Epfn showed ectopic overexpression in the dental mesenchyme of BIO-treated molars. Moreover, alkaline phosphatase activity increased in the dental mesenchyme, again suggesting aberrant, ectopic mesenchymal cell differentiation. Finally, Bmp4 downregulated Epfn expression during dental morphogenesis.
CONCLUSIONS
We suggest the presence of a positive feedback loop wherein Epfn and β-catenin activate each other. The balance of the expression of these two molecules is essential for proper tooth development. We propose a possible link between Wnt, Bmp, and Epfn that would critically determine the correct patterning of dental cusps and the differentiation of odontoblasts and ameloblasts.
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.3389/fcell.2016.00025
- PMID 27066482
- Persistent URL
- https://folia.unifr.ch/global/documents/48559
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