Authors – Elena M. Popa , Marcela Buchtova and Abigail S. Tucker
Reference – Popa, E.M., Buchtova, M. and Tucker, A.S., 2019. Revitalising the rudimentary replacement dentition in the mouse. Development, 146(3), p.dev171363.
Background
Most mammals develop two sets of teeth (deciduous and permanent), a condition known as diphyodonty. In contrast, mice are monophyodont and only produce one set. Despite this, mice briefly form a structure called the rudimentary successional dental lamina (RSDL), which resembles the tissue responsible for generating replacement teeth in other species but normally regresses before forming a new tooth. Previous research suggests that two key factors—Wnt/β-catenin signalling and the stem cell marker Sox2—play important roles in tooth development and regeneration.
Aim
This study aimed to understand why mice cannot naturally replace their teeth and to investigate whether activating specific molecular pathways could “reawaken” the RSDL and induce the formation of new teeth.
Methods
The researchers compared tooth development in mice with that in diphyodont animals to identify important molecular differences. They then used genetic techniques to artificially activate Wnt/β-catenin signalling in Sox2-expressing cells in mouse embryos. Additional experiments included culturing tooth tissues, isolating the RSDL, and analysing gene expression patterns to determine whether new tooth structures formed and developed normally.
Results
The study found that the mouse RSDL contains Sox2-positive cells but lacks Wnt signalling, which appears to prevent it from forming replacement teeth. When Wnt/β-catenin signalling was experimentally activated, the RSDL showed increased cell proliferation and produced new tooth germs on the inner side of existing molars. These new structures displayed key features of normal tooth development, including the presence of enamel knot signalling centres and the ability to mineralise in culture.
The researchers also observed a regulatory relationship between Sox2 and Wnt signalling: activating Wnt reduced Sox2 expression, suggesting a negative feedback loop. Additionally, removing the original tooth allowed the RSDL to develop into a new tooth germ, indicating that existing teeth may suppress replacement through inhibitory signals.
Conclusion
This study demonstrates that mice retain a hidden potential to form replacement teeth, but this ability is normally suppressed by molecular factors—particularly the absence of Wnt signalling and inhibition from existing teeth. By activating the appropriate signalling pathways, it is possible to stimulate new tooth formation. These findings provide important insights into the evolution of tooth replacement and suggest potential future applications in regenerative dentistry.
Research Summary Written By: Rufus Mathew, King’s College London – BDS 3