Figure 3 Developmental skeletogenesis Figure 3 | Developmental skeletogenesis. Longitudinal views depicting key steps of endochondral bone formation in mouse limbs. a | Prx1+ progenitors from lateral plate mesoderm proliferate to populate the emerging limb bud. b | Cells nearest the centre undergo mesenchymal condensation, express Col2a1 as they enter a chondrogenic differentiation program, and deposit a cartilage template. c | to d | Differentiating cells upregulate Col10a1 as they become hypertrophic, which triggers local formation of a bone collar and vascularization of the cartilage template. Invading blood vessels deliver an influx of haematopoietic cells that give rise to osteoclasts which excavate the cartilage template, and Osx1+ osteoblast progenitors and other blood cell types that populate the newly formed marrow cavity. d | A longitudinal growth axis is established when vascularization and osteoclast-mediated resorption bisect the presumptive skeletal element, producing two growth plates with opposing directionality. A perpendicular growth axis is driven by periosteal osteoblasts and allows the bone to grow in width. e | Within the remodelled cartilage template, bone-forming osteoblasts are derived from Osx1+ cells arriving with the invading vasculature, as well as hypertrophic Col10a1+ chondroctyes that transdifferentiate as they exit the growth plate into the marrow cavity. As bones grow in length and width, a second wave of vascularization forms the secondary ossification centres. f | Mature endochondral bone. Additional information about developmental skeletogenesis and a summary of genetic evidence for involvement of the bone morphogenetic protein pathway in developmental skeletogenesis can be found in the text and in Supplementary information S1,S2,S3,S4,S5 (tables). Gamer, L. W. & Rosen, V. et al. (2016) BMP signalling in skeletal development, disease and repair Nat. Rev. Endocrinol. doi:10.1038/nrendo.2016.12