title: Axonal wiring of guanylate cyclase-D-expressing olfactory neurons is dependent on neuropilin 2 and semaphorin 3F.
abstract: The olfactory system of the mouse includes several subsystems that project axons from the olfactory epithelium to the olfactory bulb. Among these is a subset of neurons that do not express the canonical pathway of olfactory signal transduction, but express guanylate cyclase-D (GC-D). These GC-D-positive (GC-D+) neurons are not known to express odorant receptors. Axons of GC-D+ neurons project to the necklace glomeruli, which reside between the main and accessory olfactory bulbs. To label the subset of necklace glomeruli that receive axonal input from GC-D+ neurons, we generated two strains of mice with targeted mutations in the GC-D gene (Gucy2d). These mice co-express GC-D with an axonal marker, tau-beta-galactosidase or tauGFP, by virtue of a bicistronic strategy that leaves the coding region of the Gucy2d gene intact. With these strains, the patterns of axonal projections of GC-D+ neurons to necklace glomeruli can be visualized in whole mounts. We show that deficiency of one of the neuropilin 2 ligands of the class III semaphorin family, Sema3f, but not Sema3b, phenocopies the loss of neuropilin 2 (Nrp2) for axonal wiring of GC-D+ neurons. Some glomeruli homogeneously innervated by axons of GC-D+ neurons form ectopically within the glomerular layer, across wide areas of the main olfactory bulb. Similarly, axonal wiring of some vomeronasal sensory neurons is perturbed by a deficiency of Nrp2 or Sema3f, but not Sema3b or Sema3c. Our findings provide genetic evidence for a Nrp2-Sema3f interaction as a determinant of the wiring of axons of GC-D+ neurons into the unusual configuration of necklace glomeruli.
authors.affiliation: The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Walz
authors.forename: Paul
authors.initials: P
authors.lastname: Feinstein
authors.forename: Mona
authors.initials: M
authors.lastname: Khan
authors.forename: Peter
authors.initials: P
authors.lastname: Mombaerts
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian; D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016297:Mutagenesis, Site-Directed; D009415:Nerve Net / Q000196:embryology* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D039943:Neuropilin-2 / Q000502:physiology*; D009832:Olfactory Nerve / Q000196:embryology* / Q000378:metabolism*; D009928:Organ Specificity; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D039961:Semaphorins / Q000235:genetics; D019147:Vomeronasal Organ / Q000196:embryology / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D039943:Neuropilin-2; D011956:Receptors, Cell Surface; C526269:Sema3b protein, mouse; C491229:Sema3f protein, mouse; D039961:Semaphorins; D006162:Guanylate Cyclase; C484774:Gucy2d protein, mouse