Cellular basis of accelerated whole-tooth regeneration.

Area of Science:

• Developmental Biology
• Evolutionary Biology
• Comparative Anatomy

Background:

• Mammals typically lack lifelong tooth replacement, hindering understanding of dental regeneration mechanisms.
• Cichlid fishes exhibit one-for-one tooth replacement, providing a model for studying dental regeneration tempo and mode.

Purpose of the Study:

• To investigate the tempo of dental replacement in cichlid fish after tooth plucking.
• To identify cell populations, gene expression changes, and cellular interactions during accelerated tooth regeneration.

Main Methods:

• Tooth plucking in cichlid fish species with divergent dentitions.
• Single-nucleus RNA sequencing (snRNA-seq) to profile cellular and molecular changes.
• Analysis of gene expression signatures and inferred cellular trajectories.

Main Results:

• Cichlid species accelerated tooth replacement over threefold after plucking.
• snRNA-seq revealed distinct gene expression profiles and cellular interactions across four time points.
• Differential signaling pathways (Collagen, BMP, MMP, Semaphorin, Slit-Robo) were identified, highlighting roles in immune response, odontogenesis, vascularization, and nerve pathfinding.

Conclusions:

• This study elucidates the cellular and molecular dynamics of tooth regeneration in cichlids.
• The findings provide a comparative framework for understanding dental regeneration across vertebrates.
• Identified signaling pathways offer potential targets for future research in regenerative dentistry.