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Zonal organization of the mouse olfactory systems
Umeå University, Faculty of Medicine, Molecular Biology.
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.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 911
Keyword [en]
Molecular biology, olfactory, vomeronasal, gene expression, zone, organization, behavior
Keyword [sv]
Molekylärbiologi
National Category
Biochemistry and Molecular Biology
Research subject
Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-336ISBN: 91-7305-706-1 (print)OAI: oai:DiVA.org:umu-336DiVA: diva2:143143
Public defence
2004-10-01, Major Groove, 6L, Norrlands Universitetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2004-11-22 Created: 2004-11-22 Last updated: 2010-01-29Bibliographically approved
List of papers
1. Evidence for gradients of gene expression correlating with zonal topography of the olfactory sensory map
Open this publication in new window or tab >>Evidence for gradients of gene expression correlating with zonal topography of the olfactory sensory map
Show others...
2001 (English)In: Molecular and Cellular Neuroscience, ISSN 1044-7431, E-ISSN 1095-9327, Vol. 18, no 3, 283-295 p.Article in journal (Refereed) Published
Abstract [en]

Signals regulating diversification of olfactory sensory neurons to express odorant receptors and other genes necessary for correct assembly of the olfactory sensory map persist in the olfactory epithelium of adult mouse. We have screened for genes with an expression pattern correlating with the topography odorant receptor-expression zones. The Msx1 homeobox gene and a semaphorin receptor (Neuropilin-2) showed graded expression patterns in the olfactory epithelium. The gradients of Msx1 and Neuropilin-2 expression in basal cells and neurons, respectively, correlated with expression of a retinoic acid-synthesizing enzyme (RALDH2) in lamina propria. A BMP-type I receptor (Alk6) showed a reverse gradient of expression in the supporting cells of the epithelium. Considering known functions of identified genes in cell specification and axon guidance this suggests that zonal division of the olfactory sensory map is maintained, during continuous neurogenesis, as a consequence of topographic counter gradients of positional information. Copyright 2001 Academic Press.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-5321 (URN)10.1006/mcne.2001.1019 (DOI)11591129 (PubMedID)
Available from: 2006-09-19 Created: 2006-09-19 Last updated: 2017-12-14Bibliographically approved
2. NQO1 activity in the main and the accessory olfactory systems correlates with the zonal topography of projection maps
Open this publication in new window or tab >>NQO1 activity in the main and the accessory olfactory systems correlates with the zonal topography of projection maps
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.

Keyword
DT-diaphorase, gene expression, odorant receptors, olfactory, sensory map, vomeronasal
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-4156 (URN)10.1111/j.0953-816X.2004.03331.x (DOI)15128404 (PubMedID)
Available from: 2004-11-22 Created: 2004-11-22 Last updated: 2017-12-14Bibliographically approved
3. Vomeronasal Phenotype and Behavioral Alterations in Gαi2 Mutant Mice
Open this publication in new window or tab >>Vomeronasal Phenotype and Behavioral Alterations in Gαi2 Mutant Mice
2003 (English)In: Current Biology, ISSN 0960-9822, E-ISSN 1879-0445, Vol. 13, no 14, 1214-1219 p.Article in journal (Refereed) Published
Abstract [en]

Several social and reproductive behaviors are under the influence of the vomeronasal (VN) organ; VN neurons detect odorous molecules emitted by individuals of the same species. There are two types of VN neurons, and these differ in their expression of chemosensory receptors and G protein subunits. The significance of this dichotomy is largely unknown. VN neurons express high levels of either G alpha i2 or G alpha o. A mouse line carrying a targeted disruption of the G alpha i2 gene offered the opportunity for studying the effects of a lack of receptor signaling through the heterotrimeric Gi2 protein in one VN cell type. As a consequence of this deficiency, the number of VN neurons that normally express G alpha i2 is decreased by half. These residual neurons are defective in eliciting a response in their target neurons in the accessory olfactory bulb. Moreover, G alpha i2 mutant mice show alterations in behaviors for which an intact VN organ is known to be important. Display of maternal aggressive behavior is severely blunted, and male mice show significantly less aggression toward an intruder. However, male mice show unaltered sexual-partner preference. This suggests that the two types of VN neurons may have separate functions in mediating behavioral changes in response to chemosensory information.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-4157 (URN)10.1016/S0960-9822(03)00452-4 (DOI)12867032 (PubMedID)
Available from: 2004-11-22 Created: 2004-11-22 Last updated: 2017-12-14Bibliographically approved
4. Inhibition of retinoid signaling in mature vomeronasal sensory neurons: postnatal degradation of a population of neurons and behavioral characterization
Open this publication in new window or tab >>Inhibition of retinoid signaling in mature vomeronasal sensory neurons: postnatal degradation of a population of neurons and behavioral characterization
Manuscript (Other academic)
Identifiers
urn:nbn:se:umu:diva-4158 (URN)
Available from: 2004-11-22 Created: 2004-11-22 Last updated: 2010-01-13Bibliographically approved

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