Dermal bone remodelling by invasive osteoblasts evolved in stem gnathostomes

Summary The evolutionary origin of the human face can be traced to the earliest vertebrates with a dermal skeleton in which canonical skeletal tissues and cell types arose. To elucidate its developmental evolution we performed genetic mosaic labelling, 3D single cell analysis and fluorescent matrix birthdating in vivo . We discover a common lineage origin of endothelial cells and osteoblasts and de novo vasculogenesis (not angiogenesis) as the dominant mechanism. Inside the spongy (cancellous) layer, invasive OPN+/RUNX2+ osteoblasts establish two orthogonal collagen scaffolds, remodel them by directional secretion of matrix metalloproteinases and employ controllers of hydroxyapatite crystal resorption previously considered to be osteoclast-specific. Such intercalary biomineralization, comprising cellular sheet and volumetric biomineral expansion, renders all layers malleable even during postnatal stages. We trace this mechanism to bone ontogenies of the earliest skeletonizing vertebrates and resolve cell/tissue homologies controversial for almost two centuries. Our new model also has implications for bone matrix bioengineering and cancer osteomimicry that might replay some of these ontogenetic processes.