Aberrant sensory innervation of the olfactory bulb in neuropilin-2 mutant mice.
The mammalian olfactory system consists of two anatomically segregated structures, the main olfactory system and the vomeronasal system, which each detect distinct types of chemical stimuli in the environment. During development, sensory neurons establish precise axonal connections with their respective targets within the olfactory bulb. The specificity of the odorant or vomeronasal receptor expressed by the sensory neuron is crucial in this process, yet it is less clear which of the more conventional axon guidance molecules are involved. Here, we show that neuropilin-2, a coreceptor for some of the class 3 semaphorins, is expressed in subpopulations of olfactory and vomeronasal sensory neurons. We generated a knock-out mutation in the neuropilin-2 gene by gene targeting in embryonic stem cells. Neuropilin-2 mutant mice exhibit profound and distinct effects on target innervation within the olfactory bulb. In the main olfactory system, axons of olfactory sensory neurons penetrate into the deeper layers of the main olfactory bulb. In the vomeronasal system, axonal fasciculation within the vomeronasal nerve is affected; some axons are misrouted and innervate glomeruli in an ectopic domain of the accessory olfactory bulb.
Walz
Andreas
A
The Rockefeller University, New York, New York 10021, USA.
Rodriguez
Ivan
I
Mombaerts
Peter
P
D000818:Animals; D001369:Axons / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis; D018390:Gene Targeting; D049452:Green Fluorescent Proteins; D006579:Heterozygote; D006720:Homozygote; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D009421:Nervous System Malformations / Q000235:genetics / Q000473:pathology*; D019581:Neuropil / Q000473:pathology; D039942:Neuropilin-1; D009830:Olfactory Bulb / Q000378:metabolism / Q000473:pathology*; D018034:Olfactory Receptor Neurons / Q000473:pathology; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D040121:Semaphorin-3A; D013234:Stem Cells; D019147:Vomeronasal Organ / Q000294:innervation / Q000473:pathology; D016875:tau Proteins / Q000235:genetics
D002352:Carrier Proteins; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; C488217:Sema3a protein, mouse; D040121:Semaphorin-3A; D016875:tau Proteins; D039942:Neuropilin-1; D049452:Green Fluorescent Proteins