Fig. 4. Cell death in Vegfa and Hif1a conditional knockout (CKO) bones. Histological sections of E16.5 Vegfa CKO humerus (B) show areas of cell death (arrow), unlike the unaffected bone (A). Compared with the femur and tibia of unaffected mice (C), the E18.5 Vegfa CKO bones (D) were misshapen with extensive regions of dead cells in the center of the bones, starting at the articular surface and continuing through the resting to the proliferating zones of chondrocytes and ending in a misshapen growth plate (arrows). Histological sections of unaffected (E) and Hif1a CKO (F) femur and tibia at E15.5 show misshapen bones with extensive regions of dead cells in the center of the bones (arrowheads).