Axonal wiring of guanylate cyclase-D-expressing olfactory neurons is dependent on neuropilin 2 and semaphorin 3F

作者：Walz Andreas; Feinstein Paul; Khan Mona; Mombaerts Peter^*

来源：Development, 2007, 134(22): 4063-4072.

DOI：10.1242/dev.008722

• guanylate cyclase
• semaphorin
• neuropilin
• olfactory bulb
• VNO
• necklace glomeruli

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.

• 出版日期2007-11-15