Neuropilin-2 regulates the development of select cranial and sensory nerves and hippocampal mossy fiber projections

Neuropilin-1 and neuropilin-2 bind differentially to different class 3 sema phorins and are thought to provide the ligand-binding moieties in receptor complexes mediating repulsive responses to these semaphorins. Here, we have studied the function of neuropilin-2 through analysis of a neuropilin-2 mu tant mouse, which is viable and fertile. Repulsive responses of sympathetic and hippocampal neurons to Sema3F but not to Sema3A are abolished in the m utant. Marked defects are observed in the development of several cranial ne rves, in the initial central projections of spinal sensory axons, and in th e anterior commissure, habenulo-interpeduncular tract, and the projections of hippocampal mossy fiber axons in the infrapyramidal bundle. Our results show that neuropilin-2 is an essential component of the Sema3F receptor and identify key roles for neuropilin-2 in axon guidance in the PNS and CNS.