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  • 1.
    Norlin, Marianne
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Alenius, Mattias
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Gussing, Fredrik
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Hägglund, Maria
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Vedin, Viktoria
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Bohm, Staffan
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Evidence for gradients of gene expression correlating with zonal topography of the olfactory sensory map2001In: Molecular and Cellular Neuroscience, ISSN 1044-7431, E-ISSN 1095-9327, Vol. 18, no 3, p. 283-295Article in journal (Refereed)
    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.

  • 2.
    Norlin, Marianne
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Vedin, Viktoria
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Bohm, Staffan
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Berghard, Anna
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Odorant-dependent, spatially restricted induction of c-fos in the olfactory epithelium of the mouse.2005In: Journal of Neurochemistry, ISSN 0022-3042, E-ISSN 1471-4159, Vol. 96, no 6, p. 1594-602Article in journal (Refereed)
    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.

  • 3.
    Vedin, Viktoria
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Molecular and functional anatomy of the mouse olfactory epithelium2006Doctoral 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.

  • 4.
    Vedin, Viktoria
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Berghard, Anna
    Regional differences in turnover of olfactory sensory neurons in the adultManuscript (Other academic)
  • 5.
    Vedin, Viktoria
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Eriksson, Björn
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Berghard, Anna
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Organization of the chemosensory neuroepithelium of the vomeronasal organ of the Scandinavian moose Alces alces2010In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1306, p. 53-61Article in journal (Refereed)
    Abstract [en]

    A functional vomeronasal organ is present in most land-living vertebrates, but not in all. Studies in a limited number of mammals have shown that stimulation of the vomeronasal neurons by odorous cues from conspecifics can lead to changes in innate behaviors in association to e.g. mating and aggression. Given the role of the organ in detecting odorous molecules important for species-specific communication, investigations of the structure of the vomeronasal organ within the mammalian group are warranted. Wild Scandinavian moose (Alces alces) is an even-toed ungulate (order: Artiodactyla) and the largest representative of the deer family Cervidae. This is the first study of the vomeronasal organ of a deer species that includes immunohistochemistry. The gross anatomy of the tubular vomeronasal. organ of moose was investigated including a nasopalatine duct that may allow for entrance of odorous substances from the oral and nasal cavities. The histology of the neuroepithelial part, in moose of both sexes, appeared overall similar to that of representatives of other Artiodactyla families. Basement membrane, structural epithelial cells, glia and sensory neurons were analyzed by expression of specific markers. The results suggest that the vomeronasal neuroepithelium of even-toed ungulates is more similar in organization to that of carnivores than e.g. rodents with regard to the relative number of sensory neurons and presence of functionally distinct populations of neurons. (C) 2009 Elsevier B.V. All rights reserved.

  • 6.
    Vedin, Viktoria
    et al.
    Umeå University, Faculty of Science and Technology, Molecular Biology (Faculty of Science and Technology).
    Molander, Marie
    Umeå University, Faculty of Science and Technology, Molecular Biology (Faculty of Science and Technology).
    Bohm, Staffan
    Umeå University, Faculty of Medicine, Molecular Biology (Faculty of Medicine).
    Berghard, Anna
    Umeå University, Faculty of Science and Technology, Molecular Biology (Faculty of Science and Technology).
    Regional differences in olfactory epithelial homeostasis in the adult mouse2009In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 513, no 4, p. 375-384Article in journal (Refereed)
    Abstract [en]

    The olfactory sensory neurons in the nasal cavity of the adult mouse are organized into a few regions that differ in their molecular properties, as several classes of genes show regional expression. Most renowned is the fact that expression of each of hundreds of different odorant receptor genes is limited to one such region, or zone, of the olfactory neuroepithelial sheet. Zone differences are in place at birth, as exemplified here by the expression of neuronal progenitor marker Foxg1. We herein describe that an adult pattern showing regional differences in neurogenesis develops during the first few weeks of postnatal life which, e.g., is reflected in the temporal and regional regulation of the neuronal progenitor marker Ascl1. The most dorsomedial zone shows significantly fewer cells in S-phase in the adult but not in newborn mice by two different measures. Moreover, we show that there are regional differences in the relative differentiation, cell survival, and thickness of the olfactory epithelium. These findings are compatible with the view that zones are inherently distinct and that such differences contribute to generate regional differences in cellular homeostasis that in turn may modulate the capacity of a region to adjust to extrinsic influence.

  • 7.
    Vedin, Viktoria
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Slotnick, Burton
    Berghard, Anna
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Zonal ablation of the olfactory sensory neuroepithelium of the mouse: effects on odorant detection.2004In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 20, no 7, p. 1858-1864Article in journal (Refereed)
    Abstract [en]

    Olfactory sensory neurons that express a specific odorant receptor, out of a thousand different, are unevenly distributed within, but restricted to one of four zones of the neuroepithelial sheet in the nasal cavity in the mouse. This zonal restriction of neurons expressing the same odorant receptor may have consequences, e.g. in case of localized injury. We found that the chemical dichlobenil can produce specific and permanent ablation of neurons in odorant receptor expression zone 1, while a higher dichlobenil dose causes reversible toxicity in neighboring zones. In behavior tests, mice lacking part of the olfactory epithelium had an increased detection threshold concentration of two-four orders of magnitude for some odorants but not others, resembling the phenomenon of specific hyposmia. This indicates that the broad tuning properties of single odorant receptors and their large number cannot fully compensate for loss of the receptor(s) with the highest sensitivity for a particular odorant.

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