ArticlePloS one2016
Plakophilin-1, a Novel Wnt Signaling Regulator, Is Critical for Tooth Development and Ameloblast Differentiation.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 32 citations in OpenAlex.
- Challenges of Studying Amelogenesis in Gene-Targeted Mouse Models.International journal of molecular sciences · 2025Review
- Plakophilin 1 in cancer: context-dependent dualism, subcellular dynamics, and therapeutic targeting.Frontiers in cell and developmental biology · 2025Review
- Development of a novel ex vivo organ culture system to improve preservation methods of regenerative tissues.Scientific reports · 2023Article
- Integration of Single-Cell RNA- and CAGE-seq Reveals Tooth-Enriched Genes.Journal of dental research · 2022Article
- A catenin of the plakophilin-subfamily, Pkp3, responds to canonical-Wnt pathway components and signals.Biochemical and biophysical research communications · 2021Article
- Role and application of stem cells in dental regeneration: A comprehensive overview.EXCLI journal · 2021Review
- Desmosomes as Signaling Hubs in the Regulation of Cell Behavior.Frontiers in cell and developmental biology · 2021Review
- G protein-coupled receptorThe Journal of biological chemistry · 2020Article
- Article
- Expression Patterns ofFrontiers in cell and developmental biology · 2020Article
- Single-Cell RNA-Sequencing From Mouse Incisor Reveals Dental Epithelial Cell-Type Specific Genes.Frontiers in cell and developmental biology · 2020Article
- Advances of Wnt signalling pathway in dental development and potential clinical application.Organogenesis · 2019Review
- The transcription factor NKX2-3 mediates p21 expression and ectodysplasin-A signaling in the enamel knot for cusp formation in tooth development.The Journal of biological chemistry · 2018Article
- The human PKP2/plakophilin-2 gene is induced by Wnt/β-catenin in normal and colon cancer-associated fibroblasts.International journal of cancer · 2018Article
- Nephronectin plays critical roles in Sox2 expression and proliferation in dental epithelial stem cells via EGF-like repeat domains.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Tooth morphogenesis is initiated by reciprocal interactions between the ectoderm and neural crest-derived mesenchyme, and the Wnt signaling pathway is involved in this process. We found that Plakophilin (PKP)1, which is associated with diseases such as ectodermal dysplasia/skin fragility syndrome, was highly expressed in teeth and skin, and was upregulated during tooth development. We hypothesized that PKP1 regulates Wnt signaling via its armadillo repeat domain in a manner similar to β-catenin. To determine its role in tooth development, we performed Pkp1 knockdown experiments using ex vivo organ cultures and cell cultures. Loss of Pkp1 reduced the size of tooth germs and inhibited dental epithelial cell proliferation, which was stimulated by Wnt3a. Furthermore, transfected PKP1-emerald green fluorescent protein was translocated from the plasma membrane to the nucleus upon stimulation with Wnt3a and LiCl, which required the PKP1 N terminus (amino acids 161 to 270). Localization of PKP1, which is known as an adhesion-related desmosome component, shifted to the plasma membrane during ameloblast differentiation. In addition, Pkp1 knockdown disrupted the localization of Zona occludens 1 in tight junctions and inhibited ameloblast differentiation; the two proteins were shown to directly interact by immunoprecipitation. These results implicate the participation of PKP1 in early tooth morphogenesis as an effector of canonical Wnt signaling that controls ameloblast differentiation via regulation of the cell adhesion complex.
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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.