Fig. 6. Analysis of Vegfa expression in Hif1a conditional knockout (CKO) mice. Histological sections of E15.5 tibia of unaffected (A) and Hif1a CKO mice (B) reveal a delay in vessel invasion into the Hif1a CKO primary ossification center (arrowheads). Vegfa expression in the primary ossification center of unaffected tibia at E15.5 (G) shows expression in hypertrophic chondrocytes but no detectable expression in the epiphysis. At E18.5 (E), the expression of Vegfa in the hypertrophic zone is maintained and it is possible to detect a moderate level of Vegfa expression in the epiphysis (arrows). At E15.5 in the primary ossification center of tibia there is no apparent difference in Vegfa expression in the hypertrophic chondrocytes of unaffected (C) and Hif1a CKO mice (D), although the shape of the hypertrophic region is abnormal in the Hif1a CKO section (D). At E18.5 (F) the expression of Vegfa in the Hif1a CKO is dramatically decreased. At this stage, the extensive cell death in the Hif1a tissue makes it almost impossible to see any hypertrophic zone of chondrocytes and all remaining viable cells are proliferating Col2a1-positive cells (H).