Fig. 11. Two-step model of cartilage vascularization. At E13.5, high levels of VEGF are expressed in the perichondrium and surrounding tissues; this stimulates vascular ingrowth into this area. At E14.5, VEGF expression is reduced in the perichondrial regions as expression in the hypertrophic region begins. At E15.5, high-level expression of VEGF in the hypertrophic zone leads to chondroclast/osteoclast recruitment and vascular invasion. At E17.5, VEGF expression is maintained in the hypertrophic zone after a marrow cavity is established.