Immunolocalization of the Factors Related to Wnt Signaling Pathway in Developing Rat Molar

Abstract

In the Wnt/β-catenin signaling pathway, Wnt signal is transmitted to glycogen synthase kinase-3β (GSK-3β) through Dishevelled (Dvl), GSK-3β activity is inhibited, β-catenin phosphorylation is inhibited by the inactive-type GSK-3β, and β-catenin is transferred to the nucleus where it interacts with lymphoid enhancing factor (LEF)/T-cell factor (TCF), a transcription factor, which is considered to induce and regulate gene expression. In tooth development, it has been reported that Wnt and LEF are expressed at the earliest stage and are related to tooth development, but there are few reports on the situation at a later stage, and there have been no reports on Dvl and GSK-3β. In this study, we immunohistochemically examined the distribution of factors related to the Wnt/β-catenin signaling pathway, Wnt10, Dvl, GSK-3β, p-GSK-3β (inactive GSK-3β), and β-catenin, using serial sections of rat first molar germ to investigate the role of the Wnt signaling pathway in tooth germ development and tooth morphogenesis. Immunostaining for anti-Wnt10, anti-Dvl, anti-GSK-3β, anti-p-GSK-3β, and anti-β-catenin showed positive reactions at the inner enamel epithelium of tooth germ and weakly positive reactions at the dental papilla cells in contact with the inner enamel epithelium at embryonic day 19. At 8 days after birth, immunostaining for every antibody showed positive reactions for preameloblasts and preodontoblasts and more clearly positive reactions for secretory ameloblasts and odontoblasts. These results suggest that Wnt10, Dvl, GSK-3β, p-GSK-3β, and β-catenin are distributed in inner enamel epithelium, secretory ameloblasts, and odontoblasts, and that the Wnt/β-catenin signaling pathway via Dvl and p-GSK-3β is involved in these cells. In addition, for each of the factors, differentiated secretory cells showed more clearly positive reactions than undifferentiated cells; therefore, we conclude that the Wnt10 signaling pathway may be involved in differentiation to ameloblasts and odontoblasts, as well as secretory functions of ameloblasts and odontoblasts.

Does age estimated from teeth forming in different early life periods show differential discrepancy with known age?

“…Wnt (Moriguchi, Yamada, Miake, & Nitta, 2011; Suomalainen & Thesleff, 2010; Yang et al, 2018), transforming growth factor (TGF) (Tummers & Thesleff, 2009; Yang et al, 2018), bone morphogenetic protein (Bmp) (O'Connell et al, 2012; Tummers & Thesleff, 2009), fibroblast growth factor (FGF) (Jarvinen et al, 2006; Tummers & Thesleff, 2009), and sonic hedgehog (Shh) (Jarvinen et al, 2006; Tummers & Thesleff, 2009) are all signaling pathways that have been found to play regulatory roles during tooth formation. The abnormal functioning of any of these signaling pathways could result in developmental anomalies, in particular during the process of amelogenesis where their proper functioning is required for the secretion of enamel matrix by ameloblasts during the secretory stage of tooth development (Moriguchi et al, 2011; Yang et al, 2018). When the activation or inhibition of these pathways prevents normal ameloblast function during this stage, the extent of enamel formation is reduced or arrested (Tummers & Thesleff, 2009), the potential outcome of which could be delayed crown formation and reduced tooth length.…”

The human EDAR 370V/A polymorphism affects tooth root morphology potentially through the modification of a reaction–diffusion system

“…In the initiation of root formation, Wnt10a and β-catenin are expressed in preodontoblasts, odontoblasts and HERS, which are distributed similar to the reverse-spotted pattern in our simulation 66 – 69 . Dkk1, which likely acts as the inhibitor in the reaction–diffusion system, is also expressed in these cells 68 , 70 , 71 . Therefore, the localizations of both Wnt10a and Dkk1 are consistent with our pure reaction–diffusion model under the condition of a low saturation value of the activator ( u max ) (Fig.…”

Immunolocalization of SP6, LEF1 and Associated Factors in the Tooth Germ of Rat Molars

“…Then, ß-catenin binds to a transcription factor, LEF1/ TCF, to induce gene expressions 1,2) . During tooth development, Wnt-10a and -10b are expressed in the mesenchyme 3) and epithelium 4) , respectively, thus being involved in differentiation into odontoblasts and ameloblasts and their functions through ßcatenin 5) . Particularly, Wn-10a is expressed in preodontoblasts and secretory odontoblasts, being involved in dentinogenesis and mineralization through dentin sialophosphoprotein (DSPP) 3) .…”