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NQO1 activity in the main and the accessory olfactory systems correlates with the zonal topography of projection maps
Umeå University, Faculty of Medicine, Molecular Biology.
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
2004 (English)In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 19, no 9, 2511-2518 p.Article in journal (Refereed) Published
Abstract [en]

The mouse olfactory epithelium (OE) is divided into spatial zones, each containing neurons expressing zone-specific subsets of odorant receptor genes. Likewise, the vomeronasal (VN) organ is organized into apical and basal subpopulations of neurons expressing different VN receptor gene families. Axons projecting from the different OE zones and VN subpopulations form synapses within circumscribed regions in the glomerular layer of the olfactory bulb (OB) and accessory olfactory bulb (AOB), respectively. We here show that mature neurons in one defined zone selectively express NADPH:quinone oxidoreductase (NQO1), an enzyme that catalyses reduction of quinones. Immunohistochemistry and in situ hybridization analyses show non-overlapping expression of NQO1 and the Rb8 neural cell adhesion molecule (RNCAM/OCAM) in OE and axon terminals within glomeruli of the OB. In addition, NQO1 immunoreactivity reveals selective, zone-specific axon fasciculation in the olfactory nerve. VN subpopulations do not show complementary patterns of RNCAM and NQO1 immunoreactivity, instead both genes are co-expressed in apical VN neurons that project to the rostral AOB. These results indicate that one division of both the accessory and the main olfactory projection maps are composed of sensory neurons that are specialized to reduce environmental and/or endogenously produced quinones via an NQO1-dependent mechanism. The role of NQO1 in bioactivation of quinoidal drugs also points to a connection between zone-specific NQO1 expression and zone-specific toxicity of certain olfactory toxins.

Place, publisher, year, edition, pages
2004. Vol. 19, no 9, 2511-2518 p.
Keyword [en]
DT-diaphorase, gene expression, odorant receptors, olfactory, sensory map, vomeronasal
National Category
Medical and Health Sciences
URN: urn:nbn:se:umu:diva-4156DOI: 10.1111/j.0953-816X.2004.03331.xPubMedID: 15128404OAI: diva2:143140
Available from: 2004-11-22 Created: 2004-11-22 Last updated: 2010-04-20Bibliographically approved
In thesis
1. Zonal organization of the mouse olfactory systems
Open this publication in new window or tab >>Zonal organization of the mouse olfactory systems
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Animals survey their environment for relevant odorous chemical compounds by means of the olfactory system. This system is in most vertebrates divided into a main and accessory olfactory system with two specialized neuroepithelia, the olfactory and the vomeronasal epithelium, respectively. The sensory neurons reside in these epithelia and together the neurons have an extraordinary sensitivity and are capable of detecting a vast number of different chemical molecules. After processing the chemical information, behavior may be altered. The information about a chemicals structure is deconstructed into a format that the brain may process. This is facilitated by organizing sensory neurons into a map and that the individual neuron responds only to one chemical feature. The sensory maps appear to have zones with different neuronal subpopulations. This thesis is addressing the fact that establishment, maintenance and function of these zones are unknown.

We identify a gene (NQO1) to be selectively expressed in defined zone of the olfactory and the vomeronasal epithelia, respectively. NQO1-positive and negative axons segregate within the olfactory nerve and maintain a zonal organization when reaching olfactory bulb target neurons. These results indicate that one zone of both the accessory and the main olfactory projection maps is composed of sensory neurons specialized in reducing environmental and/or endogenously produced quinones via an NQO1-dependent mechanism.

In addition, we have identified genes expressed in a graded manner that correlates with the dorsomedial-ventrolateral zonal organization of the olfactory epithelia. Considering the known functions of identified genes in establishment of cell specificity and precise axonal targeting, we suggest that zonal division of the primary olfactory systems is maintained, during continuous neurogenesis, as a consequence of topographic counter gradients of positional information.

The vomeronasal sensory neurons (VSN) are organized into an apical and a basal zone. The zones differ in expression of e.g. chemosensory receptor families and Gα protein subunits (Gαi2 and Gαo). We have analyzed transgenic mice (OMP-dnRAR) in which the VSNs are unresponsive to the function of one of the genes identified herein (RALDH2). The phenotype observed suggests that endogenous produced retinoic acid is selectively required for postnatal survival of neurons in the Gαo-positive zone. Analyses of another mouse line target deleted in the Gαi2 gene (Gαi2 mutant) reveal a cellular phenotype that is opposite to that of OMP-dnRAR mice. Consequently in these mice, the apical Gαi2-positive zone is reduced whereas VSNs in the basal zone are not affected.

Several social and reproductive behaviors are under the influence of the vomeronasal organ. We have analyzed some behavioral consequences of having deficient neurons that corresponds to either of the two zones. We propose that cues important for aggressive behavior are detected by apical vomeronasal zone, while cues detected by both apical and basal VSNs influence gender preference behavior.

Place, publisher, year, edition, pages
Umeå: Molekylärbiologi, 2004. 116 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 911
Molecular biology, olfactory, vomeronasal, gene expression, zone, organization, behavior, Molekylärbiologi
National Category
Biochemistry and Molecular Biology
Research subject
Molecular Biology
urn:nbn:se:umu:diva-336 (URN)91-7305-706-1 (ISBN)
Public defence
2004-10-01, Major Groove, 6L, Norrlands Universitetssjukhus, Umeå, 09:00 (English)
Available from: 2004-11-22 Created: 2004-11-22 Last updated: 2010-01-29Bibliographically approved

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