Fig. 10. (A) Schematic representation of the rib ossification process. At embryonic day 12, the entire rib consists of cartilage. Starting at embryonic day 14, a growth plate is established and ossification begins, proceeding ventrally towards the sternum. The ossification process continues until the mice reach adulthood and an area of permanent costochondral cartilage (arrow) remains throughout life. Red rectangle indicates area represented in B,C. Cartilage is blue and bone is brown. (B) Schematic representation of rib growth plate and chondrocyte differentiation. (a) Around E14, the rib cartilage template becomes invaded by blood vessels, osteoblasts and osteoclasts, and a growth plate is established. Chondrocytes, which are not part of the growth plate, express Col2. (b) When mice reach the age of 2 weeks, chondrocytes in the center of the rib cartilage become hypertrophic and express Col10 (red arrow). (c) When mice reach skeletal maturity, this hypertrophic region expands towards the periphery of the perichondrium, while the growth plate becomes smaller and replacement of cartilage with bone stops. (C) Schematic representation of rib chondrocyte differentiation in Ext2 heterozygotes. (a) During early stages of development, no differences can be observed in between rib cartilage of wild-type and Ext2^+/– mice. (b) By the age of 2 weeks, however, nodules of Col10-expressing chondrocytes are being formed near the perichondrium as a result of premature hypertrophic differentiation. (c) Formation of an exostosis could be the result of the growth plate moving past a nodule, creating a disruption in bone collar formation. Alternatively, the passage of the growth plate might provide vascularization to the nodule and initiate the bony outgrowth of an exostosis. D, dorsal; V, ventral.