The vertebrate lymphatic system consists of lymphatic vessels, which collect fluid from the tissues and return it to the blood, and lymph nodes, which are involved in immune defence. Lymphatic vessels, like blood vessels, form a complex vascular network, but what guides the development of this network? According to Stefan Schulte-Merker and co-workers, arteries provide crucial guidance cues to the lymphatic endothelial cells (LECs) that form the lymphatic network in the zebrafish trunk (see p. 2653). Using transgenic zebrafish lines that allow the direct visualization of arteries, veins and lymphatic vessels in single embryos, the researchers show first that intersegmental lymphatic vessels (ISLVs) in the zebrafish trunk align with arterial intersegmental vessels (aISVs) but not with venous intersegmental vessels. Then, using time-lapse confocal imaging, they show that LECs migrate exclusively along aISVs and that LEC migration is blocked in zebrafish mutants that lack aISVs. Together, these data reveal a crucial role for arteries in LEC guidance; future research will unravel the mechanism underlying this guidance.

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