1. Beijing Laboratory of Oral Health; Capital Medical University School of Stomatology, Beijing, China.
2. Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing, China.
3. Department of Oral Basic Science, School of Stomatology, Dalian Medical University, Dalian, China.
4. Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medical Sciences, Beijing, China.
5. Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha, China.
6. Academician Workstation for Oral-Maxillofacial Regenerative Medicine, Central South University, Changsha, China.
*These authors (Wenwen Guo and Xiaoyu Lin) contribute equally to this work.
The fibroblast growth factor (FGF) pathway plays an important role in epithelial-mesenchymal interactions during tooth development. Nevertheless, how the ligands, receptors, and antagonists of the FGF pathway are involved in epithelial-mesenchymal interactions remains largely unknown. Miniature pigs exhibit tooth anatomy and replacement patterns like those in humans and hence can serve as large animal models. The present study investigated the spatiotemporal expression patterns of critical genes encoding FGF ligands (FGF3, FGF4, FGF7, and FGF9), antagonists (SPRY2 and SPRY4) and receptors (FGFR1, FGFR2, and FGFR3) in the third deciduous molars of miniature pigs at the cap (embryonic day 40, E40), early bell (E50), and late bell (E60) stages. The results of in situ hybridization (ISH) with tyramide signal amplification and of qRT-PCR analysis revealed increased expression of FGF7, FGFR1, FGFR2, and SPRY4 in dental epithelium and of FGF7 and FGFR1 in mesenchyme from E40 to E50. In contrast, the results revealed decreased expression of FGF3, FGF4, FGF9, and FGFR3 in dental epithelium and of FGF4, FGF9, FGFR2, and FGFR3 in the mesenchyme from E40 to E60. Mesenchyme signals of FGF3, FGF4, FGF7, SPRY2, FGFR2, and FGFR3 were concentrated in the odontoblast layer from E50 to E60. The distinct expression patterns of these molecules indicated elaborate regulation during dental morphogenesis. Our results provide a foundation for further investigation into fine-tuning dental morphogenesis and odontogenesis by controlling interactions between dental epithelium and mesenchyme, thus promoting tooth regeneration in large mammals.
Keywords: miniature pig, tooth development, deciduous molar, fibroblast growth factor, dental epithelium, dental mesenchyme