BMP Signaling Regulates Mesenchymal Stem Cells for Incisor Homeostasis

Objectives: BMP signaling performs multiple essential functions during craniofacial development. In this study, we used the adult mouse incisor as a model to uncover how BMP signaling maintains tissue homeostasis and regulates mesenchymal stem cell (MSC) fate by mediating WNT and FGF signaling.

Methods: Lineage tracing was used to analyze co-localization of active BMP signaling and the progeny of Gli1+ cells in one-month-old Gli1-Cre^ERT2;tdTomato mice at one day, one week and four weeks after tamoxifen induction. Morphological analysis was performed to examine the incisors of Gli1-Cre^ERT2;Bmpr1a^fl/fl mice. RNAScope and qPCR analysis were performed to explore the cellular mechanism of incisor defects in these mice.

Results: We observed significantly shorter incisors and a severe defect of the proximal region of the incisor four weeks after tamoxifen induction in adult Gli1-Cre^ERT2;Bmpr1a^fl/fl mice. In addition, we found increased proliferation and upregulated ectopic WNT and FGF signaling activity in the preodontoblast region in mutant mice. Moreover, we confirmed that compromised BMP signaling in preodontoblasts leads to a diminished Gli1+ MSC population.

Conclusions: Our study highlights how BMP signaling pathway plays multiple roles in regulating tissue homeostasis, namely balancing proliferation and differentiation as well as maintaining the MSC population.