Tissue interactions are indispensable for cavity formation and disc separation in the temporomandibular joint.

Purpose: Our previous study found that in the temporomandibular joint (TMJ) of the K14-cre; Ctnnb1ex3f mouse embryo, the morphogenesis of glenoid fossa was interrupted by the dislocated condyle. This observation suggested that the formation of the glenoid fossa required tissue interactions with condylar mesenchyme. The purpose of this study was to clarify if the interactions between other components are essential for TMJ morphogenesis.Materials and methods: We examined the gross morphology, histology, cell proliferation, and gene expression in the developing TMJ of K14-cre; Ctnnb1ex3f mice by whole-mount bone and cartilage staining, Azon staining, BrdU labeling, and in situ hybridization, respectively.Results: In K14-cre; Ctnnb1ex3f mice, the zygomatic arch was misconnected to the mandibular bone by ectopic bone formation, which disrupted the attachment of temporalis to the mandibular bone and joint capsule formation. Although the initiation and differentiation of the condylar cartilage were slightly impacted, the K14-cre; Ctnnb1ex3f TMJ lacked joint cavities and separated disc, suggesting that the tissue interactions between the joint capsule and the TMJ were indispensable for the cavity formation and disc separation. The ectopic activation of Gli2 in the cells occupying the cavities, and the enhanced PTHrP transcription in the condylar perichondrium of the K14-cre; Ctnnb1ex3f TMJ suggested that the disrupted interactions between the joint capsule and the TMJ impaired cavity formation and disc separation by altering Hh signaling.Conclusion: Joint capsule formation was essential for cavity formation and disc separation during TMJ development.

Mesenchymal Wnt/ß-catenin signaling induces Wnt and BMP antagonists in dental epithelium.

Previous studies indicated that the elevated mesenchymal Wnt/ß-catenin signaling deprived dental mesenchyme of odontogenic fate. By utilizing ex vivo or pharmacological approaches, Wnt/ß-catenin signaling in the developing dental mesenchyme was suggested to suppress the odontogenic fate by disrupting the balance between Axin2 and Runx2. In our study, the Osr2-creKI; Ctnnb1ex3f mouse was used to explore how mesenchymal Wnt/ß-catenin signaling suppressed the odontogenic fate in vivo. We found that all of the incisor and half of the molar germs of Osr2-creKI; Ctnnb1ex3fmice started to regress at E14.5 and almost disappeared at birth. The expression of Fgf3 and Msx1 was dramatically down-regulated in the E14.5 Osr2-creKI; Ctnnb1ex3f incisor and molar mesenchyme, while Runx2transcription was only diminished in incisor mesenchyme. Intriguingly, in the E14.5 Osr2-creKI; Ctnnb1ex3f incisor epithelium, the expression of Noggin was activated, while Shh was abrogated. Similarly, the Wnt and BMP antagonists, Ectodin and Noggin were also ectopically activated in the E14.5 Osr2-creKI; Ctnnb1ex3f molar epithelium. Recombination of E13.5 Osr2-creKI; Ctnnb1ex3f molar mesenchyme with E10.5 and E13.5 WT dental epithelia failed to develop tooth. Taken together, the mesenchymal Wnt/ß-catenin signaling resulted in the loss of odontogenic fate in vivo not only by directly suppressing odontogenic genes expression but also by inducing Wnt and BMP antagonists in dental epithelium.