Expression patterns of desmosome family members during tooth development and the role of Desmocollin-3 in cytodifferentiation of stratum intermedium

Abstract

Objective

Desmocollin-3 (Dsc3), a desmosomal cadherin, is critical in maintaining epithelial cohesion and integrity. Despite its recognized function in skin and mucosal epithelium, its contribution to tooth development remains poorly understood. The study aims to identify stratum intermedium (SI)-specific markers using single-cell RNA-sequence (scRNA-seq) and to investigate the functional role of Dsc3 in maintaining SI cell integrity and differentiation.

Design

In this study, we pursued the marker genes of SI cells using scRNA-seq analysis of post-natal day 12 molar. Furthermore, we examined the role of the SI marker gene using dental epithelial cell line SF2.

Results

We found that desmosome family genes are highly expressed in SI cluster and among them, Dsc3 showed specific expression in SI cluster. Knockdown of Dsc3 in the SF2 epithelial cell line led to significantly smaller cell size, indicating impaired epithelial differentiation. The expression of SI marker genes was suppressed by the knockdown of Dsc3 with a marked loss of tight junction protein Tjp1 (ZO-1), indicating disrupted intercellular junctions and impaired epithelial barrier function. This disruption correlated with altered expression of key ameloblast differentiation markers, suggesting a failure in proper ameloblast lineage commitment, highlighting a disruption in the SI’s ability to support ameloblast lineage specification.

Conclusion

These findings indicate that Dsc3 is essential for SI structural integrity and its signaling support to ameloblasts.