Extended Data Figure 1: Schematic representation of key findings.

Organization and role of growing vessels in the regulation of osteogenesis in postnatal long bone. Endothelial columns, which are embedded between segments of forming trabecular bone in the metaphysis, are interconnected by arches at their distal end. Blind-ended, lumen-containing protrusions extend from arches towards growth plate chondrocytes, a key source of VEGF-A. Endothelial Notch signalling promotes endothelial cell proliferation and vessel growth in bone, which is the opposite of its role in other tissues. Notch activity in endothelial cells is also required for endothelial Noggin expression, controls the differentiation of perivascular osteoprogenitor cells and thereby osteogenesis. Endothelial Notch signalling and Noggin also promote chondrocyte maturation and hypertrophy, which affects angiogenesis through VEGF-A expression. These signalling interactions between different cell types couple angiogenesis and osteogenesis.