Role of the Wnt signaling molecules in the tooth

Abstract

Wnt signaling plays a central role in many processes during embryonic development and adult homeostasis. At least 19 types of Wnt ligands, receptors, transducers, transcription factors, and antagonists have been identified in mammals. Two distinct Wnt signaling pathways, the canonical signaling pathway and the noncanonical signaling pathway, have been described. Some Wnt signaling pathway components are expressed in the dental epithelium and mesenchyme during tooth development in humans and mice. Functional studies and experimental analysis of relevant animal models confirm the effects of Wnt signaling pathway on the regulation of developing tooth formation and adult tooth homeostasis. Mutations in some Wnt signaling pathway components have been identified in syndromic and non-syndromic tooth agenesis. This review provides an overview of progress in elucidating the role of Wnt signaling pathway components in the tooth and the resulting possibilities for therapeutic development.

Keywords: Canonical Wnt; Hypodontia; Oligodontia; Periodontal tissue; Tooth; Tooth agenesis; Tooth development; Wnt signaling.

Figure 1

The canonical Wnt signaling pathway. The secreted Frizzled-related protein (sFRP) family or Wise bind to Wnt proteins, leading to inhibition of the interaction between Wnt and the Frizzled receptor. Sclerostin or Dickkopf (DKK) binds to lipoprotein receptor-related proteins (LRP) 5/6 to inhibit Wnt signaling. Cytosolic accumulation of β-catenin in response to a canonical Wnt signal is a crucial step in the signaling pathway. Left: In the absence of Wnt ligand, β-catenin associates with the destruction complex composed of Axin, adenomatous polyposis coli (APC), casein kinase (CK) 2, and glycogen synthase kinase (GSK)-3. GSK-3 phosphorylates β-catenin, inducing rapid degradation of β-catenin via the ubiquitin/proteasome pathway. Right: The canonical Wnt signaling is initiated by the binding of the Wnt ligand to Frizzled and LRP5/6. Subsequently, Wnt ligand blocks β-catenin degradation, allowing transportation to the nucleus, where β-catenin interacts with the transcription factor T-cell-specific factor (TCF) and activates target gene expression.