Neuropilin-1 (Npn-1) is a receptor for both semaphorin 3A (Sema3A) and vascular endothelial growth factor 165 (VEGF 165 ). To understand the role Npn-1 plays as a receptor for these structurally and functionally unrelated ligands, we set out to identify structural features of Npn-1 that confer binding to Sema3A or VEGF 165 . We constructed Npn-1 variants containing deletions within the "a" A complex but ordered series of axon guidance decisions during development is critical for the establishment of nervous system structure and function (1). The vertebrate vascular network is similarly complex, with interconnecting conduits that extend throughout the body that are often in close anatomical proximity to nerve pathways (2). Recent evidence suggests that at least some of the same ligand-receptor systems coordinate development of both the nervous system and the cardiovascular system. For example, Eph receptors and their ligands, the ephrins, were first characterized as mediators of repulsive guidance events crucial for correct navigation of neuronal growth cones and migrating neural crest cells (3, 4). Their unexpected role in blood vessel formation was revealed when mutant mice that lacked either ephrin B2 or its cognate receptor EphB4 were shown to die during embryogenesis due to cardiovascular dysfunction (5, 6). Consistent with this observation, ephrin B2 and EphB4 were shown to have a reciprocal expression patterns in arterial and venous endothelial cells (6).Another example of a cell surface receptor whose function is required for development of both the cardiovascular and nervous systems is neuropilin-1 (Npn-1).

The two most abundant secreted isoforms of vascular endothelial growth factor A (VEGF 165