Fig. 2. Histological study of wild-type and VEGF^120/120 mice identifies marked differences in skeletal elements during development. At E14.5, the hypertrophic zone is larger in wild-type (A) than in VEGF^120/120 (B) tibia and fibula. At E15.5, blood vessel invasion into the hypertrophic cartilage can be observed in wild-type mice (C, arrow) but not in VEGF^120/120 mice (D, arrow). (E-H) At E16.5, bone marrow and bone trabeculae are present in wild-type mice (E,G) but there is a significant delay at this stage in VEGF^120/120 mice (F,H), with blood vessel invasion occurring only in the most central region of the diaphysis. t, tibia; r, radius; f, fibula; u, ulna. (I,J) At E17.5, the tibial VEGF^120/120 growth plate (J) displays a much longer hypertrophic zone than the wild-type growth plate (I). (K,L) At E16.5, wild-type calvarial bones (K) appear thicker than those in VEGF^120/120 mice (L) (b, brain; arrow indicates calvarial bone). In Fig. 2A,B,E-J the extent of the hypertrophic zone is indicated by a bracket.