Developmental evidence for the evolutionary origins of the mammalian TMJ disc

The mammalian jaw joint between the dentary bone of the lower jaw and the squamosal/temporal bone of the upper jaw is a mammalian evolutionary innovation that enables complex movements essential for chewing and speaking. It comprises the mandibular condyle, the glenoid (mandibular) fossa, and an interposed fibrocartilaginous disc. The disc is critical for joint function, and its pathology underlies several temporomandibular disorders (TMD), which can affect up to a third of adult and elderly patients. The mammalian jaw joint is proposed to have evolved to stabilize the existing primary jaw joint, found in all non-mammalian jawed vertebrates, acting as a buttress for the lower jaw against the upper to prevent jaw dislocation. The origin of the disc is less well understood, but it has been hypothesized to have evolved either from the top layers of the fibrocartilaginous condyle, or as an independent structure, potentially evolved from an existing tendon.

To resolve these relationships, the condyle and disc were analysed during murine development to shed light on their molecular and cellular identity during formation of the joint. Using Bulk RNA-seq we demonstrate that the forming temporomandibular joint (TMJ) disc exhibited a developmental trajectory distinct from that of the mandibular condyle, with Lgr5 expression serving as a marker of the developing disc from early developmental stages. Clonal tracing of cells at the interface between the condyle and disc, using Pcag-Cre^ER;Confetti mice, further demonstrated that the disc cells formed a distinct compartment compared to the superficial layers of the condyle. Notably, disc identity was preserved in Wnt1-Cre; Sox9fl/fl mutants where the condyle failed to form.

Together, these findings establish the TMJ disc as having a distinct molecular and cellular identity, initiating independently from the condyle, while sharing many features in common with a tendon. Together these findings support the TMJ disc as evolving from a tendon rather than from the condyle.