Meckel's cartilage breakdown offers clues to mammalian middle ear evolution.

A key transformation in mammalian ear evolution was incorporation of the primary jaw joint of premammalian synapsids into the definitive mammalian middle ear of living mammals. This evolutionary transition occurred in two-steps, starting with a partial or "transitional" mammalian middle ear in which the ectotympanic and malleus were still connected to the mandible by an ossified Meckel's Cartilage (MC), as observed in many Mesozoic mammals. This was followed by MC breakdown, freeing the ectotympanic and the malleus from the mandible and creating the definitive mammalian middle ear. Here we report novel findings on the role of chondroclasts in MC breakdown, shedding light on how therian mammals lost MC connecting the ear to the jaw. Genetic or pharmacological loss of clast cells in mice and opossums leads to persistence of embryonic MC beyond juvenile stages, with MC ossification in mutant mice. The persistent MC causes a distinctive postnatal groove on the mouse dentary. This morphology phenocopies the ossified MC and Meckelian groove observed in Mesozoic mammals. Clast cell recruitment to MC is not observed in reptiles, where MC persists as a cartilaginous structure. We hypothesize that ossification of MC is an ancestral feature of mammaliaforms, and that a shift in the timing of clast cell recruitment to MC prior to its ossification is a key developmental mechanism for the evolution of the definitive mammalian middle ear in extant therians.