Researchers uncover gene teamwork behind tooth root formation

During craniofacial development, cranial neural crest cells give rise to the dental mesenchyme, and developmental pathways help guide how these cells proliferate and differentiate during root formation. The genes Gli2 and Gli3 are involved in one such pathway, but their precise interaction during root development had remained unclear.

Co-author Dr Xianglong Han, a clinical professor at the National Clinical Research Center for Oral Diseases at West China Hospital of Stomatology of Sichuan University, explained in a press release that the team examined the separate and combined roles of Gli2 and Gli3 in root development by selectively inactivating either one or both genes in root progenitor cells. They found that inactivating Gli2 alone had little effect, whereas inactivation of Gli3 led to shortened roots, reduced alveolar bone formation and delayed eruption.

When both genes were inactivated, severe root defects occurred, and root length was reduced by nearly half compared with controls. The results suggest that Gli2 and Gli3 work together to regulate root development. Without these genes, progenitor cells in the dental mesenchyme showed reduced proliferation and failed to differentiate properly into odontoblasts, periodontal ligament cells or osteoblasts.

The team also found that disruption of both genes affected the transforming growth factor beta pathway, which is involved in cell differentiation and tissue formation. When the researchers activated this pathway in mice, root length, alveolar bone formation and cell differentiation were partly restored. Senior author Prof. Junjun Jing, a researcher at the National Clinical Research Center for Oral Diseases, said that identifying this link between cell communication pathways could create new possibilities for designing targeted therapies in regenerative dentistry and craniofacial medicine.

The study, titled “Gli2 and Gli3 synergistically mediate HH-TGF-β crosstalk in mesenchymal progenitor cells to orchestrate tooth root morphogenesis”, was published online on 12 March 2026 in the International Journal of Oral Science.