Neuropilins are receptors for class 3 secreted semaphorins, most of which c
an function as potent repulsive axon guidance cues. We have generated mice
with a targeted deletion in the neuropilin-2 (Npn-2) locus. Many Npn-2 muta
nt mice are viable into adulthood, allowing us to assess the role of Npn-2
in axon guidance events throughout neural development. Npn-P is required fo
r the organization and fasciculation of several cranial nerves and spinal n
erves. In addition, several major fiber tracts in the brains of adult mutan
t mice are either severely disorganized or missing. Our results show that N
pn-2 is a selective receptor for class 3 semaphorins in vivo and that Npn-1
and Npn-2 are required for development of an overlapping but distinct set
of CNS and PNS projections.