Ptip is essential for tooth development via regulating Wnt pathway

Epigenetic regulation plays important role in stem cell maintenance. Ptip was identified as epigenetic regulator, but the role in dental progenitor cells remains unclear.

Dental mesenchymal progenitor cells were targeted by Sp7-icre and visualized in mTmG; Sp7-icre mice. The Ptip^f/f; Sp7-icre mice were generated and the phenotype of incisors and molars were shown by micro-computerized tomography, scanning electron microscope, hematoxylin & eosin staining, and immunofluorescence. Dental mesenchymal progenitor cells were sorted by fluorescence-activated cell sorting from lower incisors and RNA sequencing was performed.

The Sp7-icre targets dental mesenchymal progenitor cells in incisors and molars. The Ptip^f/f; Sp7-icre mice showed spontaneous fractures in the cusp of upper incisors and lower incisors at 3 weeks (w), compensative overgrowth of lower incisors at 1 month (M), and overgrowth extended to the outside at 2 M. The molars showed shortened roots. The functions of odontoblasts and dental mesenchymal progenitor cells were impaired. Mechanically, loss of Ptip activates the Wnt pathway and upregulates the expression of Wls in dental mesenchymal progenitor cells. Also, the regenerative ability of lower incisors was significantly impaired.

We first demonstrated that Ptip was crucial for tooth development via regulating Wnt signaling.