The Epithelial-Mesenchymal Interaction Plays a Role in the Maintenance of the Stem Cell Niche of Mouse Incisors via Fgf10 and Fgf9 Signaling

Abstract

The continuous eruption of mouse incisors throughout life is maintained by adult stem cells in the apical end. In these teeth, the continuous expression of Fgf10 in the mesenchyme plays a role in the maintenance of the epithelial stem cell compartment, referred to as the "apical bud." However, little is known about the epithelial signaling that induces and maintains Fgf10 expression. Focusing on the epithelial-mesenchymal interaction during tooth development, we thoroughly investigated candidates expressed in the apical bud. In situ hybridization and immunostaining showed that Fgf9 mRNA and protein were detected in the basal epithelium, stellate reticulum, and inner enamel epithelium of the apical bud. Recombinant Fgf9 protein stimulated cell proliferation in cultures of apical end mesenchyme. Furthermore, Fgf9- releasing beads inhibited apoptosis in mesenchymal tissue cultures and maintained the expression of Fgf10. On the other hand, Fgf10-releasing beads induced Fgf9 expression in cultures of apical buds. Taken together, these results suggest that the stem cell niche in growing incisors is maintained by an epithelial mesenchymal interaction via Fgf9 and Fgf10 signaling.