Pontocerebellar axon guidance: neuropilin-1- and semaphorin 3A-sensitivity gradients across basilar pontine nuclei and semaphorin 3A variation across cerebellum.

To assess the role of semaphorin 3A (Sema3A) and its receptor component neuropilin-1 (Npn-1) in pontocerebellar axon guidance, we compared the distributions of Sema3A, Npn-1, and DiI-labeled pontocerebellar axons in neonatal mouse cerebellum. Between embryonic day 18 and birth there was a large increase in Npn-1 expression in the basilar pontine nuclei (BPN), the major source of pontocerebellar axons. Sema3A expression in cerebellum also increased at this time. In the BPN, Npn-1 and the response of axons to Sema3A were graded with high Npn-1 and Sema3A responsiveness rostrally and lower levels caudally. The Npn-1 gradient was not smooth and cells with higher and lower expression were interspersed. Between birth and postnatal day 5, pontocerebellar axons projected to lobules of the hemispheres, including those with low to moderate levels of Sema3A, but did not enter regions with high levels of Sema3A, including the flocculus and much of the vermis. These results suggest that varying neuropilin levels on BPN axons, which correlated with their varying responses to Sema3A, combined with varying Sema3A levels across cerebellum, may contribute to guiding subsets of BPN axons to their distinct target regions within cerebellum.