BMP activity regulates mesenchymal lineage commitment and tooth root initiation

Objectives: Postnatal tooth development occurs mainly in the apical region where roots form. This region contains a distinct mesenchymal stem cell (MSC) population, namely stem cells of the apical papilla (SCAPs). Despite their in vitro MSC characteristics, how SCAPs undergo odontogenic lineage commitment in vivo during development remains unclear. Because BMP signaling is an important regulator of osteo-/odontogenic differentiation of dental mesenchymal stem cells in vitro, we hypothesize that BMP signaling may also regulate the odontogenic differentiation of SCAPs in vivo.
Methods: We investigated molecular markers to identify SCAPs in vivo. We then utilized a transgenic mouse model to disrupt BMP signaling in apical mesenchymal cells and their derivatives in vivo in order to investigate the functional requirement of BMP signaling in their fate determination.
Results: We have identified SCAPs critical for postnatal tooth development in vivo. Loss of BMP function leads to failure of the SCAPs to activate their differentiation program. RNAseq analysis showed a down-regulation of several transcriptional factors associated with early craniofacial development in the apical mesenchyme of Bmp mutant mice.
Conclusions: Our results demonstrate that BMP signaling is indispensable for the in vivo odontogenic lineage commitment of MSCs during tooth morphogenesis.