Fig. 2. Reduced angiogenesis in Vegfa conditional knockout (CKO) bones. Histology of unaffected and Vegfa CKO mice identifies marked differences in skeletal elements during development. In tibia and fibula at E15.5 in unaffected mice (A), blood vessel invasion into the hypertrophic cartilage and marrow cavity can be observed (arrowheads), while no invasion can be seen into hypertrophic cartilage in the Vegfa CKO mice (B). CD31 immunostaining of tibia at E16.0 in unaffected mice (C) shows vessels throughout the periosteum and in the marrow cavity. In the Vegfa CKO mice (D), there are vessels in the periosteum but no apparent invasion into the hypertrophic zone. In the radius and ulna at E16.5 in unaffected (E) mice, bone marrow and bone trabeculae are present below the hypertrophic zone (arrowhead). In Vegfa CKO mice the growth plate contains a much longer hypertrophic zone (F, arrowhead). At E18.5, unaffected ribs (G) contain a shorter hypertrophic zone. In contrast, the Vegfa CKO ribs contain a greatly expanded zone of hypertrophy (H, arrowhead).