Intertwined Signaling Pathways Governing Tooth Development: A Give-and-Take Between Canonical Wnt and Shh

Abstract

Teeth play essential roles in life. Their development relies on reciprocal interactions between the ectoderm-derived dental epithelium and the underlying neural crest-originated mesenchyme. This odontogenic process serves as a prototype model for the development of ectodermal appendages. In the mouse, developing teeth go through distinct morphological phases that are tightly controlled by epithelial signaling centers. Crucial molecular regulators of odontogenesis include the evolutionarily conserved Wnt, BMP, FGF and sonic hedgehog (Shh) pathways. These signaling modules do not act on their own, but are closely intertwined during tooth development, thereby outlining the path to be taken by specific cell populations including the resident dental stem cells. Recently, pivotal Wnt-Shh interaction and feedback loops have been uncovered during odontogenesis, showing conservation in other developing ectodermal appendages. This review provides an integrated overview of the interplay between canonical Wnt and Shh throughout mouse tooth formation stages, extending from the initiation of dental placode to the fully formed adult tooth.

Establishment of inclusive single-cell transcriptome atlases from mouse and human tooth as powerful resource for dental research

“…The individually estimated gene densities can then be aggregated into a joint density for the panel of assessed genes. Determining the individual densities of well-reported DESC markers ( Sox2 , Lgr5 , Gli1 , Lrig1 , Bmi1 , Ptch1 ), together with those of the DEP indicator Sfrp5 ( Juuri et al, 2012 ) and of potential novel markers identified through deep-sequencing interrogation ( Pcp4 , Pknox2 , Zfp273 , Spock1 ( Krivanek et al, 2020 )) ( Supplementary Figure S1G ), followed by their assembling into joint density, revealed putative DESC localized within the IEE-OEE and VEE-OEE clusters ( Figure 1E ), consistent with the most recent DESC projections ( Gan et al, 2020 ; Fresia et al, 2021 ; Hermans et al, 2021 ). Because a number of the applied markers may also denote DM stem cells, the weighted kernel density estimation also identified a potential stem cell cluster within the DF ( Biehs et al, 2013 ; Seidel et al, 2017 ; Hermans et al, 2021 ).…”

“…Since one of the limitations of sc transcriptomics, especially when sequenced at lower depth, is the occurrence of 'dropouts' (i.e. absence of parts of the cell's transcriptome due to low mRNA expression and/or inefficient mRNA capture (Qiu, 2020) 2020)) (Supplementary Figure S1G), followed by their assembling into joint density, revealed putative DESC localized within the IEE-OEE and VEE-OEE clusters (Figure 1E), consistent with the most recent DESC projections (Gan et al, 2020;Fresia et al, 2021;Hermans et al, 2021). Because a number of the applied markers may also denote DM stem cells, the weighted kernel density estimation also identified a potential stem cell cluster within the DF (Biehs et al, 2013;Seidel et al, 2017;Hermans et al, 2021).…”

“…One study, which also applied the Smart-seq2 platform yielding higher-depth sequencing data than 10X Genomics, was able to identify putative DESC clusters ( Krivanek et al, 2020 ). DESC have been reported to represent a mixed population, characterized by (combinations of) expressed markers such as Sox2 , Lgr5 , Gli1 , Lrig1 , Bmi1 and Ptch1 ( Seidel et al, 2010 , 2017 ; Juuri et al, 2012 ; Biehs et al, 2013 ; Sanz-Navarro et al, 2018 ; Hermans et al, 2021 ). Since one of the limitations of sc transcriptomics, especially when sequenced at lower depth, is the occurrence of ‘dropouts’ (i.e.…”

Mechanisms during Osteogenic Differentiation in Human Dental Follicle Cells

“…One cell type is derived from the ectodermal germ layer (the origin of the enamel-forming ameloblasts) and the other—dental mesoderm—is derived from neural crest cells. Tooth development generally represents an interaction between these ectodermal and mesodermal cell layers that form the three dental germ tissues: enamel organ, dental papilla (dental pulp progenitor) and dental follicle [ 5 , 6 ]. During the early stages of tooth development, the dental follicle, sometimes called the “dental sac“, forms a sac-like tissue around the other two tooth germ tissues ( Figure 1 ).…”

Role of primary cilia and Hedgehog signaling in craniofacial features of Ellis–van Creveld syndrome

“…Consequently, changes in genes (such as mutations or faulty expression) have the potential to cause a wide range of genetic disorders during the various stages of life.As alluded to earlier, EvC has the characteristic phenotype marked by abnormalities in the craniofacial hard and soft tissue structures. The cardinal role played by SHH in tooth development as early as the dental placode and bud stage have been shown(Hermans, Hemeryck, Lambrichts, Bronckaers, & Vankelecom, 2021;Li, Chatzeli, Panousopoulou, Tucker, & Green, 2016); further inhibition of the same has been shown to result in abnormal growth of the tooth buds. SHH signaling is essential for the maturation and differentiation of ameloblasts.…”