Signaling from Condyle is Required for Glenoid Fossa Formation

Objective: The temporomandibular joint (TMJ), a specialized synovial joint that is present only in mammals, consists of the glenoid fossa of the temporal bone and the mandibular condyle, and an articular disc separating these two bones. Unlike the formation of other synovial joints, which form by cleavage or segmentation within a single skeletal condensation, the TMJ develops from two distinct mesenchymal condensations and form in a unique way through different ossification processes, with glenoid fossa undergoing the intramembranous ossification and condyle the endochondral ossification. However, very little is known about TMJ morphogenesis and its underlying genetic, cellular and molecular mechanisms. Here, we studied tissue interactions between condyle and glenoid fossa during TMJ development. Methods: We used Cre-mediated tissue specific inactivation or ectopic activation of target genes to manipulate gene expression in the developing condyle of mice. Histology was used to examine morphological phenotype and in situ hybridization was used to examine gene expression. Results: We report here that inactivation of Sox9 in the neural crest derived cells causes absence of condyle, which in turn leads to failed development of glenoid fossa. In this case, glenoid fossa development initiates, but does not continue, indicating that signaling from condyle is essential for maintain glenoid forssa development. The signaling molecule Ihh is expressed in the developing concyle and is required for the articular disc formation. Over-expression of Ihh in the developing condyle also causes failed development of glenoid foss, in addition to premature hypertrophy of cartilage cells and eventually formation of a hypoplastic condyle. Conclusion: Our results demonstrate that while they develop from two distinct mesenchymal condensations and undergo different ossification processes, appropriate signaling from condyle is essential for the formation of glenoid fossa during TMJ development. (supported by NIH grant DE17792)

Keywords: TMJ development, condyle, glenoid fossa, tissue interaction