Tooth development, replacement and regeneration

Teeth serve as a powerful model to dissect epithelial-mesenchymal interaction-mediated organogenesis. While most non-mammalian vertebrates exhibit lifelong tooth renewal (polyphyodonty), mammals have largely lost this capacity and become predominantly diphyodont. Elucidating this evolutionary transition is crucial for understanding developmental constraints on regeneration, yet key mechanisms, particularly how the successional dental lamina persists and how dormant stem cell niches are reactivated, remain largely unresolved. Recent advances in lineage tracing, single-cell sequencing, multi-omics profiling and organoid models have uncovered remarkable cellular diversity and lineage potential during tooth development and homeostasis across vertebrates, reshaping our view of dental stem cell identity and its roles in tissue regeneration. In this Review, we summarize recent progress in tooth development, replacement and molecular regulation, and our current understanding of dental stem cells and organoid models, aiming to delineate a roadmap for translational tooth regeneration.