The neural and vascular systems share common guidance cues that have direct and independent signaling effects on nerves and
endothelial cells. Here, we show that zebrafish Netrin 1a directs Dcc-mediated axon guidance of motoneurons and that this
neural guidance function is essential for lymphangiogenesis. Specifically, Netrin 1a secreted by the muscle pioneers at the
horizontal myoseptum (HMS) is required for the sprouting of dcc-expressing rostral primary motoneuron (RoP) axons and neighboring axons along the HMS, adjacent to the future trajectory
of the parachordal chain (PAC). These axons are required for the formation of the PAC and, subsequently, the thoracic duct.
The failure to form the PAC in netrin 1a or dcc morphants is phenocopied by laser ablation of motoneurons and is rescued both by cellular transplants and overexpression
of dcc mRNA. These results provide a definitive example of the requirement of axons in endothelial guidance leading to the parallel
patterning of nerves and vessels in vivo.