title: Wntless regulates dentin apposition and root elongation in the mandibular molar.
abstract: Wnt signaling plays an essential role in the dental epithelium and mesenchyme during tooth morphogenesis. However, it remains unclear if Wnt ligands, produced from dental mesenchyme, are necessary for odontoblast differentiation and dentin formation. Here, we show that odontoblast-specific disruption of Wntless (Wls), a chaperon protein that regulates Wnt sorting and secretion, leads to severe defects in dentin formation and root elongation. Dentin thickness decreased remarkably and pulp chambers enlarged in the mandibular molars of OC-Cre;Wls(CO/CO) mice. Although the initial odontoblast differentiation was normal in the mutant crown, odontoblasts became cuboidal and dentin thickness was reduced. In immunohistochemistry, Wnt10a, β-catenin, type I collagen, and dentin sialoprotein were significantly down-regulated in the odontoblasts of mutant crown. In addition, roots were short and root canals were widened. Cell proliferation was reduced in the developing root apex of mutant molars. Furthermore, Wnt10a and Axin2 expression was remarkably decreased in the odontoblasts of mutant roots. Deletion of the Wls gene in odontoblasts appears to reduce canonical Wnt activity, leading to inhibition of odontoblast maturation and root elongation.
authors.affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, Chonbuk National University School of Dentistry, Jeonju, South Korea.
authors.forename: C H
authors.initials: CH
authors.lastname: Bae
authors.affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, Chonbuk National University School of Dentistry, Jeonju, South Korea.
authors.forename: T H
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, Chonbuk National University School of Dentistry, Jeonju, South Korea.
authors.forename: S O
authors.initials: SO
authors.lastname: Ko
authors.affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, Chonbuk National University School of Dentistry, Jeonju, South Korea.
authors.forename: J C
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, Chonbuk National University School of Dentistry, Jeonju, South Korea oasis@jbnu.ac.kr.
authors.forename: E S
authors.initials: ES
authors.lastname: Cho
mesh_terms: D000818:Animals; D060466:Axin Protein / Q000032:analysis; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D024042:Collagen Type I / Q000032:analysis; D003786:Dental Pulp Cavity / Q000002:abnormalities; D003804:Dentin / Q000002:abnormalities; D003810:Dentinogenesis / Q000502:physiology*; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000032:analysis; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D008963:Molar / Q000002:abnormalities / Q000254:growth & development*; D009419:Nerve Tissue Proteins / Q000032:analysis; D009804:Odontoblasts / Q000502:physiology; D009805:Odontogenesis / Q000502:physiology*; D010750:Phosphoproteins / Q000032:analysis; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D012795:Sialoglycoproteins / Q000032:analysis; D019227:Tooth Apex / Q000002:abnormalities; D019228:Tooth Crown / Q000002:abnormalities; D014092:Tooth Root / Q000002:abnormalities / Q000254:growth & development*; D051153:Wnt Proteins / Q000032:analysis; D060449:Wnt Signaling Pathway / Q000502:physiology; D055114:X-Ray Microtomography / Q000379:methods; D051176:beta Catenin / Q000032:analysis; D000099311:Dentin Sialophosphoprotein
chemical_list: D060466:Axin Protein; D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D043562:Receptors, G-Protein-Coupled; D012795:Sialoglycoproteins; D051153:Wnt Proteins; D051176:beta Catenin; D000099311:Dentin Sialophosphoprotein; C111729:Axin2 protein, mouse; C495267:CTNNB1 protein, mouse; C545200:Gpr177 protein, mouse; C484143:Wnt10a protein, mouse
keywords: Wnt signaling pathway; dentinogenesis; mice; odontoblasts; tooth development; tooth roots