Neuropilin (NRP) receptors and their class 3 semaphorin (SEMA) ligands have well-established roles in axon guidance. On , Christiana Ruhrberg and colleagues now report that these proteins also direct cranial neural crest cells (NCCs) during sensory nervous system development. Cranial NCCs differentiate into glia, bone and cartilage, but also contribute sensory neurons to the cranial ganglia, the source of nerve bundles that carry sensory information to the brain. Using double Nrp1/Nrp2 mutant mice, the authors show that the ordered positioning of these sensory neurons requires NRP1 and NRP2 and their ligands SEMA3A and SEMA3F. From these and other findings, the authors conclude that these proteins act synergistically to prevent migrating cranial NCCs from wandering into the wrong part of the head. They are also required to maintain the organisation of cranial sensory axons during development, leading the researchers to propose a model in which class 3 SEMAs act on NRP receptors both to direct cranial NCCs and to repel the axonal projections of sensory neurons.
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