BIG-2 mediates olfactory axon convergence to target glomeruli.
ABSTRACT Olfactory sensory neurons expressing a given odorant receptor converge axons onto a few topographically fixed glomeruli in the olfactory bulb, leading to establishment of the odor map. Here, we report that BIG-2/contactin-4, an axonal glycoprotein belonging to the immunoglobulin superfamily, is expressed in a subpopulation of mouse olfactory sensory neurons. A mosaic pattern of glomerular arrangement is observed with strongly BIG-2-positive, weakly positive, and negative axon terminals in the olfactory bulb, which is overlapping but not identical with those of Kirrel2 and ephrin-A5. There is a close correlation between the BIG-2 expression level and the odorant receptor choice in individual sensory neurons. In BIG-2-deficient mice, olfactory sensory neurons expressing a given odorant receptor frequently innervate multiple glomeruli at ectopic locations. These results suggest that BIG-2 is one of the axon guidance molecules crucial for the formation and maintenance of functional odor map in the olfactory bulb.
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ABSTRACT: The neural cell adhesion molecule TAG-1 has been implicated in the tangential migration of neurons of the caudal medulla and of cortical interneurons. In the former case, protein is expressed by the neurons as they migrate, and blocking its function results in altered and reduced migration in vitro. In the latter case, protein is expressed, in part, by the pathway the interneurons use to reach the cortex, and in vitro experiments propose a role for TAG-1 in this system, as well. However, the in vivo requirement of TAG-1 in these migrations has not been investigated. In this report, we analyze the developmental phenotype of TAG-1-deficient animals in these two migratory systems. We show that mutant mice have smaller lateral reticular nuclei as a result of increased cell death in the superficial migratory stream of the caudal medulla. On the other hand, the absence of TAG-1 does not affect the number, morphology, timing and routes of GABAergic interneurons that migrate from the ganglionic eminences to the cortex. Therefore, TAG-1 function is required for the survival of the neurons of some precerebellar nuclei, while it is not required for cortical interneuron migration in vivo.Developmental Biology 01/2006; 288(1):87-99. · 3.87 Impact Factor
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ABSTRACT: NB-2, a member of the contactin subgroup in the immunoglobulin superfamily, is expressed specifically in the postnatal nervous system, reaching a maximum level at 3 weeks postnatal. NB-2 displays neurite outgrowth-promoting activity in vitro. To assess its function in the nervous system, we generated mutant mice in which a part of the NB-2 gene was ablated and replaced with the tau-LacZ gene. The general appearance of NB-2-deficient mice and their gross anatomical features were normal. The LacZ expression patterns in heterozygous mice revealed that NB-2 is preferentially expressed in the central auditory pathways. In the audiogenic seizure test, NB-2-deficient mice exhibited a lower incidence of wild running, but a higher mortality rate than the wild-type littermates. c-Fos immunohistochemistry demonstrated that neural excitability induced by the audiogenic seizure test in the NB-2-deficient mice was prominently attenuated in both the dorsal and external cortices of the inferior colliculus, where enhanced neural excitability was observed in the wild-type mice. In response to pure-tone stimulation after priming, NB-2-deficient mice exhibited a diffuse and low level of c-Fos expression in the central nucleus of the inferior colliculus, which was distinctly different from the band-like c-Fos expression corresponding to the tonotopic map in the wild-type littermates. Taken together, these results suggest that a lack of NB-2 causes impairment of the neuronal activity in the auditory system.European Journal of Neuroscience 04/2003; 17(5):929-36. · 3.75 Impact Factor
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ABSTRACT: The discriminatory capacity of the mammalian olfactory system is such that thousands of volatile chemicals are perceived as having distinct odors. Here we used a combination of calcium imaging and single-cell RT-PCR to identify odorant receptors (ORs) for odorants with related structures but varied odors. We found that one OR recognizes multiple odorants and that one odorant is recognized by multiple ORs, but that different odorants are recognized by different combinations of ORs. Thus, the olfactory system uses a combinatorial receptor coding scheme to encode odor identities. Our studies also indicate that slight alterations in an odorant, or a change in its concentration, can change its "code," potentially explaining how such changes can alter perceived odor quality.Cell 04/1999; 96(5):713-23. · 31.96 Impact Factor