Methods: Two strains of transgenic mouse models were used: Notch reporter mouse strain and conditional knocking out RBP-Jkappa, the key effector of Notch pathway, using a mesenchymal specific Cre mouse strain (Collagen I alpha 2 Cre).
Results: We identified that Notch signaling is activated in the incisor mesenchyme in the incisor cervical loop region. Blocking canonical Notch signaling in the mesenchyme resulting in significant changes of the release of signaling molecules including Fgf, Hgf, Tgfb and Igf family members, from the surrounding dental mesenchyme and alveolar bone. Those factors, in turn affect dental epithelial stem cell self-renew/proliferation resulting an enlarged epithelial stem cell pool and reduced tooth epithelial cell differentiation. Essentially, losing Notch signaling in the dental mesenchymal stem cells, also caused decreased stem cell proliferation/renewal and dysfunction of odontoblasts, manifested by a dentin dysplasia phenotype.
Conclusion: Our results provide an updated insight of how different tissues and pathways work together for regulating different stem cell compartments, which is essential for new tissue generation, such as a tooth.