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Rho GTPases in ameloblast differentiation

View Article: PubMed Central - PubMed

ABSTRACT

During tooth development, ameloblasts differentiate from inner enamel epithelial cells to enamel-forming cells by modulating the signal pathways mediating epithelial–mesenchymal interaction and a cell-autonomous gene network. The differentiation process of epithelial cells is characterized by marked changes in their morphology and polarity, accompanied by dynamic cytoskeletal reorganization and changes in cell–cell and cell–matrix adhesion over time. Functional ameloblasts are tall, columnar, polarized cells that synthesize and secrete enamel-specific proteins. After deposition of the full thickness of enamel matrix, ameloblasts become smaller and regulate enamel maturation. Recent significant advances in the fields of molecular biology and genetics have improved our understanding of the regulatory mechanism of the ameloblast cell life cycle, mediated by the Rho family of small GTPases. They act as intracellular molecular switch that transduce signals from extracellular stimuli to the actin cytoskeleton and the nucleus. In our review, we summarize studies that provide current evidence for Rho GTPases and their involvement in ameloblast differentiation. In addition to the Rho GTPases themselves, their downstream effectors and upstream regulators have also been implicated in ameloblast differentiation.

No MeSH data available.


Effects of a ROCK inhibitor on ameloblasts. H–E staining of ROCK inhibitor (Y27632)-treated mouse ameloblasts shows disruption of polarity and enamel formation (A and B). Immunostaining for amelogenin and ameloblastin (C–F) shows that these proteins are no longer directionally secreted. Arrows indicate cells that do not express enamel matrix proteins. Arrowheads indicate cells that secrete enamel matrix proteins in all directions. Staining of F-actin, E-cadherin and β-catenin shows the polarized distribution of those molecules in differentiated ameloblasts (G, I and K arrows), whereas ROCK inhibition disrupts the polarized distribution (H, J and L). The figures were reproduced from the study by Otsu et al. [15]. am, ameloblasts; en, enamel; si, stratum intermedium.
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fig0020: Effects of a ROCK inhibitor on ameloblasts. H–E staining of ROCK inhibitor (Y27632)-treated mouse ameloblasts shows disruption of polarity and enamel formation (A and B). Immunostaining for amelogenin and ameloblastin (C–F) shows that these proteins are no longer directionally secreted. Arrows indicate cells that do not express enamel matrix proteins. Arrowheads indicate cells that secrete enamel matrix proteins in all directions. Staining of F-actin, E-cadherin and β-catenin shows the polarized distribution of those molecules in differentiated ameloblasts (G, I and K arrows), whereas ROCK inhibition disrupts the polarized distribution (H, J and L). The figures were reproduced from the study by Otsu et al. [15]. am, ameloblasts; en, enamel; si, stratum intermedium.

Mentions: Several organ cultures of tooth germs and transgenic (Tg) approaches have been developed to evaluate the function of RhoA-ROCK signal cascade in ameloblast differentiation and enamel formation. The inhibition of all Rho GTPase by Clostridium difficile toxin A and specific inhibition of ROCK decrease amelogenin expression in tooth germs cultured in an anterior eye chamber [14]. ROCK inhibitors also disrupt ameloblast polarity and enamel formation, and amelogenins and ameloblastins are no longer directionally secreted in cultured incisors [15], [16] (Fig. 4). ROCK inhibitors were seen to markedly affect actin, E-cadherin, and β-catenin localization in the same samples and dental epithelial cell cultures (Fig. 4). Furthermore, knockdown of ROCK expressions by siRNA in cultured dental epithelial cells affects actin organization and cell–cell adhesion and reduces the expression of E-cadherin and β-catenin mRNA [15]. Inhibition of ROCK also accelerates proliferation of dental epithelial cells [15].


Rho GTPases in ameloblast differentiation
Effects of a ROCK inhibitor on ameloblasts. H–E staining of ROCK inhibitor (Y27632)-treated mouse ameloblasts shows disruption of polarity and enamel formation (A and B). Immunostaining for amelogenin and ameloblastin (C–F) shows that these proteins are no longer directionally secreted. Arrows indicate cells that do not express enamel matrix proteins. Arrowheads indicate cells that secrete enamel matrix proteins in all directions. Staining of F-actin, E-cadherin and β-catenin shows the polarized distribution of those molecules in differentiated ameloblasts (G, I and K arrows), whereas ROCK inhibition disrupts the polarized distribution (H, J and L). The figures were reproduced from the study by Otsu et al. [15]. am, ameloblasts; en, enamel; si, stratum intermedium.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5382790&req=5

fig0020: Effects of a ROCK inhibitor on ameloblasts. H–E staining of ROCK inhibitor (Y27632)-treated mouse ameloblasts shows disruption of polarity and enamel formation (A and B). Immunostaining for amelogenin and ameloblastin (C–F) shows that these proteins are no longer directionally secreted. Arrows indicate cells that do not express enamel matrix proteins. Arrowheads indicate cells that secrete enamel matrix proteins in all directions. Staining of F-actin, E-cadherin and β-catenin shows the polarized distribution of those molecules in differentiated ameloblasts (G, I and K arrows), whereas ROCK inhibition disrupts the polarized distribution (H, J and L). The figures were reproduced from the study by Otsu et al. [15]. am, ameloblasts; en, enamel; si, stratum intermedium.
Mentions: Several organ cultures of tooth germs and transgenic (Tg) approaches have been developed to evaluate the function of RhoA-ROCK signal cascade in ameloblast differentiation and enamel formation. The inhibition of all Rho GTPase by Clostridium difficile toxin A and specific inhibition of ROCK decrease amelogenin expression in tooth germs cultured in an anterior eye chamber [14]. ROCK inhibitors also disrupt ameloblast polarity and enamel formation, and amelogenins and ameloblastins are no longer directionally secreted in cultured incisors [15], [16] (Fig. 4). ROCK inhibitors were seen to markedly affect actin, E-cadherin, and β-catenin localization in the same samples and dental epithelial cell cultures (Fig. 4). Furthermore, knockdown of ROCK expressions by siRNA in cultured dental epithelial cells affects actin organization and cell–cell adhesion and reduces the expression of E-cadherin and β-catenin mRNA [15]. Inhibition of ROCK also accelerates proliferation of dental epithelial cells [15].

View Article: PubMed Central - PubMed

ABSTRACT

During tooth development, ameloblasts differentiate from inner enamel epithelial cells to enamel-forming cells by modulating the signal pathways mediating epithelial–mesenchymal interaction and a cell-autonomous gene network. The differentiation process of epithelial cells is characterized by marked changes in their morphology and polarity, accompanied by dynamic cytoskeletal reorganization and changes in cell–cell and cell–matrix adhesion over time. Functional ameloblasts are tall, columnar, polarized cells that synthesize and secrete enamel-specific proteins. After deposition of the full thickness of enamel matrix, ameloblasts become smaller and regulate enamel maturation. Recent significant advances in the fields of molecular biology and genetics have improved our understanding of the regulatory mechanism of the ameloblast cell life cycle, mediated by the Rho family of small GTPases. They act as intracellular molecular switch that transduce signals from extracellular stimuli to the actin cytoskeleton and the nucleus. In our review, we summarize studies that provide current evidence for Rho GTPases and their involvement in ameloblast differentiation. In addition to the Rho GTPases themselves, their downstream effectors and upstream regulators have also been implicated in ameloblast differentiation.

No MeSH data available.