New Study Finds Cells That Know When, Where, and How to Grow Teeth

The ‘address’ of young dental cells could be the body’s blueprint for growing teeth and gums.

CHENGDU, SICHUAN, CHINA, October 23, 2025 /EINPresswire.com/ -- A novel study on the natural coordination of tooth development in time and space, led by Dr. Han-Sung Jung at the Yonsei University College of Dentistry, Korea, has discovered that “lingual” cells on the side of the tongue form the tooth, whereas those toward the cheek, called “buccal cells,” form the bones and gums, guided by signaling molecules like WNT and BMP. These insights could shape future modalities for tooth regeneration, replacement, and repair.

Tooth development is a dynamic process that involves the stages of the bud, the cap, and the bell, followed by root development and subsequent tooth formation. Processes such as the bud-to-cap transition are mediated by epithelial-mesenchymal interactions. In addition, the position of a cell in a developing embryo determines its fate due to the relative differences in concentration of signaling molecules and growth factors.

Scientists have long known that a single tooth develops as a small bud of outer “epithelial” cells into the deeper “mesenchymal” cells. It then curves to form a cap shape and then folds in further to form the bell shape of a mature tooth, with surrounding bone and gums. Dr. Han-Sung Jung and his team at the Yonsei University College of Dentistry, Korea, extended these findings by examining how the position of young epithelial and mesenchymal dental cells would influence what they grow into and have published their findings in International Journal of Oral Science.

Lead author Dr. Jung said that his team “performed this study to identify how positional identity along the lingual-buccal axis determines distinct developmental fates of dental mesenchyme. This research has the potential to significantly impact our understanding of tooth development,” he says.

The investigators separated the mesenchymal cells on the lingual and buccal sides at both cap and bell stages of a developing mouse embryo and -compared their gene expression profiles through RNA-seq followed by Gene Ontology enrichment analysis to understand the differences with position and time. They then transplanted the cap-stage lingual and buccal cells separately under the kidney capsule of immunocompromised mice to see what each grew into. Analysis showed that cells on the lingual side were mainly geared toward making the tooth itself and shaping its structure, while cells on the buccal side were more focused on stem cell activity, forming surrounding tissues, and supporting tooth growth and repair. Not surprisingly, only the lingual cells in the mouse kidney grew into tooth enamel.

The researchers also reported haphazardly mixing up cap-stage, tagged buccal and lingual cells of genetically engineered mice. “We were curious to know if they could find their original place and reorganize when the fluorescently labled lingual and buccal mesenchymal cells were mixed randomly, which they not only did, but the lingual cells grew into dentin to form the tooth as before. This phenomenon is called cellular self-organization,” says first author Eun-Jung Kim.

Furthermore, they have extensively studied the signalling molecules in each group and found that WNT signalling and R-spondins (Rspo1/2/4) are enriched in lingual cells, along with high proliferation, low cell death, and higher migration rate, aiding tooth formation. On the other hand, buccal cells show increased expression of BMP inhibitors, lower proliferation, higher apoptosis, and slower migration, favoring bone and surrounding tissue formation.

In conclusion, the authors proposed a model of dental cell positioning based on the lingual-buccal axis for tooth and surrounding tissue formation. The characteristics of dental mesenchymal cells were found to vary along this axis, and the fate of the tooth and surrounding tissue formation is determined by mesenchymal cells via WNT/BMP signaling. Deeper knowledge of the molecular nuances of tooth development will inspire further research in tissue engineering and regenerative medicine, which may ultimately lead to advancements in stem cell-based tooth regeneration and more effective therapeutic applications for dental restoration and repair.

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Reference
Title of original paper: Prespecified dental mesenchymal cells for the making of a tooth
Journal: International Journal of Oral Science
DOI: https://doi.org/10.1038/s41368-025-00391-7

Yini Bao
International Journal of Oral Science
2885546461 ext.
ijos@scu.edu.cn
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