ArticleDevelopment (Cambridge, England)2015
The non-canonical BMP and Wnt/β-catenin signaling pathways orchestrate early tooth development.
Article in Development (Cambridge, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 71 citations in OpenAlex.
- Foxq1-Wnt5a Axis Activation in Dental Papilla Stem Cells Promotes Odontogenesis on Acellular Matrix: A Laboratory Investigation.International endodontic journal · 2026Article
- Harnessing human tumor organoids for cancer modeling and precision therapy.Protein & cell · 2026Review
- Stem cell-driven biomedical technologies for tooth regeneration: engineering scaffolds, organoid models, and molecular targeted strategies.Stem cell research & therapy · 2026Review
- Kdf1 Regulates Molar Cusp Morphogenesis via the PI3K/AKT/mTOR Signalling Axis.Cell proliferation · 2026Article
- Spatiotemporal interplay between epithelial and mesenchymal cells drives human dentinogenesis.Nature communications · 2026Article
- Genetic Variants in DVL3 are Associated With Root Maldevelopment, Tooth Agenesis, Mesiodens, and Oral Exostoses.International dental journal · 2026Article
- Regenerative teeth induced by in vitro mesenchymal cells in mice via repressing BMP4 and activating retinoic acid/osteopontin.Cell regeneration (London, England) · 2025Article
- Timing and Graded BMP Signalling Determines Fate of Neural Crest and Ectodermal Placode Derivatives from Pluripotent Stem Cells.Biomedicines · 2024Review
- Notch Signaling Hydrogels Enable Rapid Vascularization and Promote Dental Pulp Tissue Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Smad4 is essential for epiblast scaling and morphogenesis after implantation, but nonessential before implantation.Development (Cambridge, England) · 2024Article
- Article
- Homeobox Genes in Odontogenic Lesions: A Scoping Review.Head and neck pathology · 2023Article
- Activin receptor-like kinase 3: a critical modulator of development and function of mineralized tissues.Frontiers in cell and developmental biology · 2023Review
- Review
- DNCP induces the differentiation of induced pluripotent stem cells into odontoblasts by activating the Smad/p-Smad and p38/p-p38 signaling pathways.Experimental and therapeutic medicine · 2021Article
- The effects of altered BMP4 signaling in first branchial-arch-derived murine embryonic orofacial tissues.International journal of oral science · 2021Article
- mTOR inhibitors reduce enteropathy, intestinal bleeding and colectomy rate in patients with juvenile polyposis of infancy with PTEN-BMPR1A deletion.Human molecular genetics · 2021Article
- Dual roles of TGF-β signaling in the regulation of dental epithelial cell proliferation.Journal of molecular histology · 2021Article
- Exploring the Association Between Genetic Polymorphisms in Genes Involved in Craniofacial Development and Isolated Tooth Agenesis.Frontiers in physiology · 2021Article
- Noggin inhibition of mouse dentinogenesis.Journal of oral biosciences · 2020Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
BMP and Wnt signaling pathways play a crucial role in organogenesis, including tooth development. Despite extensive studies, the exact functions, as well as if and how these two pathways act coordinately in regulating early tooth development, remain elusive. In this study, we dissected regulatory functions of BMP and Wnt pathways in early tooth development using a transgenic noggin (Nog) overexpression model (K14Cre;pNog). It exhibits early arrested tooth development, accompanied by reduced cell proliferation and loss of odontogenic fate marker Pitx2 expression in the dental epithelium. We demonstrated that overexpression of Nog disrupted BMP non-canonical activity, which led to a dramatic reduction of cell proliferation rate but did not affect Pitx2 expression. We further identified a novel function of Nog by inhibiting Wnt/β-catenin signaling, causing loss of Pitx2 expression. Co-immunoprecipitation and TOPflash assays revealed direct binding of Nog to Wnts to functionally prevent Wnt/β-catenin signaling. In situ PLA and immunohistochemistry on Nog mutants confirmed in vivo interaction between endogenous Nog and Wnts and modulation of Wnt signaling by Nog in tooth germs. Genetic rescue experiments presented evidence that both BMP and Wnt signaling pathways contribute to cell proliferation regulation in the dental epithelium, with Wnt signaling also controlling the odontogenic fate. Reactivation of both BMP and Wnt signaling pathways, but not of only one of them, rescued tooth developmental defects in K14Cre;pNog mice, in which Wnt signaling can be substituted by transgenic activation of Pitx2. Our results reveal the orchestration of non-canonical BMP and Wnt/β-catenin signaling pathways in the regulation of early tooth development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.