The presence of the vertebral column is the defining feature of all vertebrate animals. In amniote embryos, cells of the sclerotome, which derives from the somite, migrate and differentiate to give rise to chondrocytes and then to osteoblasts, which replace the existing cartilage with bone in a process known as endochondral ossification. In other vertebrates, however, ossification proceeds without the cartilage intermediate, and the developmental origin of the bone-mineralizing cells remains unclear. In this issue, Matthias Hammerschmidt and colleagues show that chordoblasts, which derive from the early notochord anlage, are required for the segmented ossification of the notochord sheath as a first step in the formation of the vertebrae. The authors use transgenic reporter assays to demonstrate that metameric subsets of chordoblasts are activated by retinoid acid (RA) in a manner highly similar to osteoblast differentiation in amniotes. Upon treatment with RA, col2a1a-expressing chordoblasts reduce the production of collagen matrix and instead increase mineralization, which leads to hyper-ossification of the notochord sheath. Selective and temporally controlled ablation of chordoblasts, or selective blockage of RA reception in chordoblasts, result in a complete absence of notochordal sheath mineralization, which cannot be rescued by exogenous RA treatment. This study makes a substantive contribution to our understanding of vertebral column formation in teleost fish and sheds light on the developmental origin of vertebral bone-mineralizing cells.
