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

Triana Marchelina; Yuta Chiba; Shinji Otake; Li Wanshu; Hiroshi Sato; Yumiko Nakashima; Asuna Sugimoto; Tsutomu Iwamoto; Aya Yamada; Kan Saito; Satoshi Fukumoto

doi:10.1016/j.archoralbio.2025.106404

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

Arch Oral Biol. 2025 Sep 24:180:106404. doi: 10.1016/j.archoralbio.2025.106404. Online ahead of print.

Authors

Affiliations

¹ Division of Pediatric Dentistry, Department of Community Social Dentistry, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.
² Division of Pediatric Dentistry, Department of Community Social Dentistry, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan. Electronic address: yuta.chiba.a8@tohoku.ac.jp.
³ Section of Pediatric Dentistry, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
⁴ Department of Pediatric Dentistry / Special Needs Dentistry, Division of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo 113-8549, Japan.
⁵ Division of Pediatric Dentistry, Department of Community Social Dentistry, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan; Section of Pediatric Dentistry, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: fukumoto@dent.kyushu-u.ac.jp.

PMID: 41016088
DOI: 10.1016/j.archoralbio.2025.106404

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.

Keywords: Cell differentiation; Desmosome; ScRNA-seq; Stratum intermedium; Tooth development.