TMJ Development and Growth Require Primary Cilia Function

Primary cilia regulate limb and axial skeletal formation and hedgehog signaling, but their roles in temporomandibular joint (TMJ) development are unknown. Thus, we created conditional mouse mutants deficient in ciliary transport protein Kif3a in cartilage. In post-natal wild-type mice, primary cilia were occasionally observed on the superior, inferior, or lateral side of condylar cells. Cilia were barely detectable in mutant chondrocytes but were evident in surrounding tissues, attesting to the specificity of chondrocyte Kif3a ablation. Mutant condyles from 3-month-old mice were narrow and flat along their antero-posterior and medio-lateral axes, were often fused with the articular disc, and displayed an irregular bony surface. The polymorphic layer in P15 mutants contained fewer Sox9-expressing chondroprogenitor cells because of reduced mitotic activity, and newly differentiated chondrocytes underwent precocious hypertrophic enlargement accompanied by early activation of Indian hedgehog (Ihh). Interestin...