Lessons on skeletal cell plasticity from studying jawbone regeneration in zebrafish

Three major mesenchymal cell types have important roles in determining the shapes of vertebrate animals: bone-producing osteoblasts, cartilage-producing chondrocytes, and fat-producing adipocytes. Although often considered discrete cell types, accumulating evidence is revealing mesenchymal cells of intermediate identities and interconversion of cell types. Such plasticity is particularly evident during adult skeletal repair. In this Review, we highlight recent work in zebrafish showing a role for hybrid cartilage-bone cells in large-scale regeneration of the adult jawbone, as well as their origins in the periosteum. An emerging theme is that the unique mechanical and signaling environment of the adult wound causes skeletal cell differentiation to diverge from the discrete lineages seen during development, which may aid in rapid and extensive regeneration of bone.