Functions of Neuropilins in Wiring the Nervous System and Their Role in Neurological Disorders

The proper wiring of the nervous system depends on an orderly series of events, beginning in embryonic development with neuronal migration, axon and dendrite development, and guidance events and continuing in postnatal development with synaptogenesis, pruning of axonal projections, and synapse refinement. In the nervous system, neuropilins function mainly with the class 3 secreted semaphorins (Sema3s) to mediate a majority of these developmental processes. Neuropilins bind to Sema3s as obligatory cell surface co-receptors and form a complex with the type A plexin family members, as well as with cell adhesion molecules and other modulatory co-receptors, to activate intracellular signaling networks that, in most cases, influence cytoskeletal dynamics and neuronal morphology. Changes to neuronal morphology are known to regulate neural connectivity and activity. In this chapter we will focus on recent discoveries of neuropilin functions, mediated by Sema3 signaling, to regulate wiring of the nervous system. In addition, we will highlight some of the emerging roles neuropilins play in neurodevelopmental and neuropsychiatric disorders.