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Odorant-dependent, spatially restricted induction of c-fos in the olfactory epithelium of the mouse.
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). (Berghard)
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). (Berghard)
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). (Bohm)
Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). (Berghard)
2005 (English)In: Journal of Neurochemistry, ISSN 0022-3042, E-ISSN 1471-4159, Vol. 96, no 6, 1594-602 p.Article in journal (Refereed) Published
Abstract [en]

Volatile odorous chemicals are detected by around a thousand different G protein-coupled odorant receptors in the mouse. We demonstrated that exposure of the behaving mouse to odorant for a few minutes led to induction of the immediate early gene c-fos for several hours in a fraction of the olfactory sensory neurones in the nasal cavity. Associated with this odorant-specific induction event was activation of extracellular-regulated kinase (ERK)1/2 that preceded increased c-fos expression. The distribution of odorant-activated neurones mimicked the scattered and spatially limited distribution of neurones expressing a single odorant receptor gene. A small change in odorant chemical structure caused a zonal shift in the spatial distribution of activated neurones, suggesting that the gene expression change resulted from specific receptor interaction. Repeated exposure to odorant or use of different concentrations did not change the pattern of c-fos induction. These results indicate that odorant-induced c-fos expression can be used to visualize odorant representations in the olfactory epithelium that reflect late cellular events regulated by adequate odorant receptor stimulation.

Place, publisher, year, edition, pages
2005. Vol. 96, no 6, 1594-602 p.
National Category
Cell Biology
URN: urn:nbn:se:umu:diva-16531DOI: 10.1111/j.1471-4159.2005.03159.xPubMedID: 15935076OAI: diva2:156204
Available from: 2007-10-05 Created: 2007-10-05 Last updated: 2012-02-18
In thesis
1. Molecular and functional anatomy of the mouse olfactory epithelium
Open this publication in new window or tab >>Molecular and functional anatomy of the mouse olfactory epithelium
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The olfactory system is important for social behaviors, feeding and avoiding predators. Detection of odorous molecules is made by odorant receptors on specialized sensory neurons in the olfactory epithelial sheet. The olfactory sensory neurons are organized into a few regions or “zones” based on the spatially limited expression of odorant receptors. In this thesis the zonal division and functional specificity of olfactory sensory neurons have been studied in the mouse. We find that zones 2-4 show overlapping expression of odorant receptors while the border between the regions that express a zone 1 and a zone 2 odorant receptor, respectively, is sharp. This result indicates that zone 1 and zones 2-4 are inherently different from each other. In cDNA screens, aimed at finding genes whose expression correlate to the zonal expression pattern of odorant receptors, we have identified a number of signaling proteins implicated in neural-tissue organogenesis in other systems. The differential expression pattern of identified genes suggests that regional organization is maintained during the continuous neurogenesis in the olfactory epithelium as a result of counter gradients of positional information. We show that the gene c-fos is induced in olfactory sensory neurons as a result of cell activation by odorant exposure. A zonal and scattered distribution of c-Fos-positive neurons resembled the pattern of odorant receptor expression and a change of odorant results in a switch in which zone that is activated. Whereas earlier studies suggest that the odorant receptors are relatively broadly tuned with regard to ligand specificity, the restricted patterns of c-Fos induction suggests that low concentrations of odorous molecules activate only one or a few ORs. Studies on olfactory detection abilities of mice with zonal-restricted lesions in the olfactory epithelium show that loss of a zone has severe effects on the detection of some odorants but not others. These findings lend support to a hypothesis that odorant receptors are tuned to more limited numbers of odorants. Regional differences in gene expression and differences in response to toxic compounds between the zones indicate that there may be differences in tissue homeostasis within the epithelium. We have found that there are differences in proliferation and survival of olfactory sensory neurons in regions correlating to receptor expression zones. Identified differences with regard to gene expression, tissue homeostasis and odorant detection show that the olfactory epithelium is divided into regions that transduce different stimulus features.

Place, publisher, year, edition, pages
Umeå: Molekylärbiologi, 2006. 71 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1047
olfactory epithelium, odorant receptor, zone, odorant, gene expression, cell specification, c-Fos, dichlobenil, olfactometry, proliferation
National Category
Biochemistry and Molecular Biology
urn:nbn:se:umu:diva-868 (URN)91-7264-138-X (ISBN)
Public defence
2006-10-06, Major Groove, 6L, Umeå Universitet, 901 87 Umeå, 09:30 (English)
Available from: 2006-09-19 Created: 2006-09-19 Last updated: 2009-10-30Bibliographically approved

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Vedin, ViktoriaBohm, StaffanBerghard, Anna
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