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Endothelial cells in 2-dimensional tissue culture are able to migrate (indicated by arrows), proliferate, and form chordlike structure. When placed in 3-dimensional culture in a collagen matrix, endothelial cells form tunnels and generate a lumen, thereby displaying properties that are considered essential for assembling the vasculature in vivo. Sacharidou and colleagues have identified a signaling complex, termed “endothelial lumen signaling complex,” which is required for tunnel and lumen formation in 3-dimensional culture of endothelial cells in collagen matrix, but not for cell migration in 2-dimensional tissue culture. Professional illustration by Marie Dauenheimer. See the commentary by Blobel on page 5128.