Research team led by Park Hae-chul and Shim Ji-suk at Korea University College of Medicine identifies key genetic regulator of dental development

A research team at the Korea University College of Medicine has uncovered a genetic mechanism responsible for delayed tooth development and impaired mineralization.

The team, led by Professor Hae-chul Park (Department of Biomedical Sciences, Korea University College of Medicine) and Professor Ji-suk Shim (Department of Dentistry, Korea University College of Medicine), investigated the role of the Axin2 gene, which encodes a negative regulator of the Wnt/β-catenin signaling pathway—a critical pathway that orchestrates cell proliferation, differentiation, and organogenesis.

Using a zebrafish model, the researchers employed CRISPR/Cas9 genome editing to delete Axin2. Zebrafish lacking this gene exhibited reduced body size, delayed eruption and growth of teeth, and markedly diminished levels of calcium and phosphorus, the essential minerals for dental hard tissue formation. Furthermore, the expression of key odontogenic marker genes was significantly downregulated.

These findings demonstrate that precise temporal regulation of Wnt signaling is indispensable for normal tooth morphogenesis and mineralization. Disruption of this pathway by genetic defects such as Axin2 deficiency results in teeth that are softer and slower to develop.

“Our results provide an important clue to understanding the genetic basis of inherited dental disorders,” said Professor Ji-suk Shim. “This study also lays the groundwork for future research in tooth regeneration and targeted therapies for developmental dental diseases.”

The study, titled “Axin2 Deficiency Causes Hypomineralization and Delayed Tooth Development”, was published in the 2025 edition of the Journal of Dental Research, one of the most prestigious journals in the field.