Semaphorin 3A is required for guidance of olfactory axons in mice

Semaphorin 3A (Sema3A) is a membrane-associated secreted protein that has c hemorepulsive properties for neuropilin-1 (npn-1)-expressing axons. Althoug h mice lacking the Sema3A protein display skeletal abnormalities and heart defects, most axonal projections in the CNS develop normally. We show here that Sema3A is expressed in the lamina propria surrounding the olfactory ep ithelium (OE) and by ensheathing cells in the nerve layer of the ventral ol factory bulb (OB) throughout development. Subsets of sensory neurons expres sing npn-1 are distributed throughout the OE and extend fibers to the devel oping OB. In wild-type mice, npn-1-positive (npn-1(+)) axons extend to late ral targets in the rostral OB and medial targets in the caudal OB, avoiding regions expressing Sema3A. In Sema3A homozygous mutant mice, many npn-1(+) axons are misrouted into and through the ventral nerve layer, beginning as early as embryonic day 13 and continuing at least until birth. At postnata l day 0, npn-1(+) glomeruli are atypically located in the ventral OB of Sem a3A(-/-) mice, indicating that aberrant axon trajectories are not corrected during development and that connections are made in inappropriate target r egions. In addition, subsets of OCAM(+) axons that normally project to the ventrolateral OB and some lactosamine-containing glycan(+) axons that norma lly target the ventral OB are also misrouted in Sema3A mutants. These obser vations indicate that Sema3A expression by ensheathing cells plays an impor tant role in guiding olfactory axons into specific compartments of the OB.