umu.sePublications
Change search
Link to record
Permanent link

Direct link
BETA
Berghard, Anna
Publications (10 of 15) Show all publications
Login, H., Håglin, S., Berghard, A. & Bohm, S. (2015). The Stimulus-Dependent Gradient of Cyp26B1+ Olfactory Sensory Neurons Is Necessary for the Functional Integrity of the Olfactory Sensory Map. Journal of Neuroscience, 35(40), 13807-13818
Open this publication in new window or tab >>The Stimulus-Dependent Gradient of Cyp26B1+ Olfactory Sensory Neurons Is Necessary for the Functional Integrity of the Olfactory Sensory Map
2015 (English)In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 35, no 40, p. 13807-13818Article in journal (Refereed) Published
Abstract [en]

Stimulus-dependent expression of the retinoic acid-inactivating enzyme Cyp26B1 in olfactory sensory neurons (OSNs) forms a dorsomedial (DM)-ventrolateral (VL) gradient in the mouse olfactory epithelium. The gradient correlates spatially with different rates of OSN turnover, as well as the functional organization of the olfactory sensory map, into overlapping zones of OSNs that express different odorant receptors (ORs). Here, we analyze transgenic mice that, instead of a stimulus-dependent Cyp26B1 gradient, have constitutive Cyp26B1 levels in all OSNs. Starting postnatally, OSN differentiation is decreased and progenitor proliferation is increased. Initially, these effects are selective to the VL-most zone and correlate with reduced ATF5 expression and accumulation of OSNs that do not express ORs. Transcription factor ATF5 is known to stabilize OR gene choice via onset of the stimulus-transducing enzyme adenylyl cyclase type 3. During further postnatal development of Cyp26B1 mice, an anomalous DMhigh-VLlow expression gradient of adenylyl cyclase type 3 appears, which coincides with altered OR frequencies and OR zones. All OR zones expand ventrolaterally except for the VL-most zone, which contracts. The expansion results in an increased zonal overlap that is also evident in the innervation pattern of OSN axon terminals in olfactory bulbs. These findings together identify a mechanism by which postnatal sensory-stimulated vitamin A metabolism modifies the generation of spatially specified neurons and their precise topographic connectivity. The distributed patterns of vitamin A-metabolizing enzymes in the nervous system suggest the possibility that the mechanism may also regulate neuroplasticity in circuits other than the olfactory sensory map.

Keywords
activity dependent, odorant receptors, olfactory sensory neurons, retinoic acid, sensory map, vitamin A
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-112309 (URN)10.1523/JNEUROSCI.2247-15.2015 (DOI)000366050900024 ()26446231 (PubMedID)
Available from: 2015-12-04 Created: 2015-12-04 Last updated: 2019-08-13Bibliographically approved
Hägglund, A.-C., Berghard, A. & Carlsson, L. (2013). Canonical Wnt/beta-Catenin Signalling Is Essential for Optic Cup Formation. PLoS ONE, 8(12), e81158
Open this publication in new window or tab >>Canonical Wnt/beta-Catenin Signalling Is Essential for Optic Cup Formation
2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, p. e81158-Article in journal (Refereed) Published
Abstract [en]

A multitude of signalling pathways are involved in the process of forming an eye. Here we demonstrate that beta-catenin is essential for eye development as inactivation of beta-catenin prior to cellular specification in the optic vesicle caused anophthalmia in mice. By achieving this early and tissue-specific beta-catenin inactivation we find that retinal pigment epithelium (RPE) commitment was blocked and eye development was arrested prior to optic cup formation due to a loss of canonical Wnt signalling in the dorsal optic vesicle. Thus, these results show that Wnt/beta-catenin signalling is required earlier and play a more central role in eye development than previous studies have indicated. In our genetic model system a few RPE cells could escape beta-catenin inactivation leading to the formation of a small optic rudiment. The optic rudiment contained several neural retinal cell classes surrounded by an RPE. Unlike the RPE cells, the neural retinal cells could be beta-catenin- negative revealing that differentiation of the neural retinal cell classes is beta-catenin-independent. Moreover, although dorsoventral patterning is initiated in the mutant optic vesicle, the neural retinal cells in the optic rudiment displayed almost exclusively ventral identity. Thus, beta-catenin is required for optic cup formation, commitment to RPE cells and maintenance of dorsal identity of the retina.

Place, publisher, year, edition, pages
Public Library of Science, 2013
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-85289 (URN)10.1371/journal.pone.0081158 (DOI)000327949300074 ()
Funder
Swedish Research CouncilSwedish Cancer Society
Available from: 2014-02-05 Created: 2014-01-31 Last updated: 2019-03-12Bibliographically approved
Berghard, A., Hägglund, A.-C., Bohm, S. & Carlsson, L. (2012). Lhx2-dependent specification of olfactory sensory neurons is required for successful integration of olfactory, vomeronasal, and GnRH neurons. The FASEB Journal, 26(8), 3464-3472
Open this publication in new window or tab >>Lhx2-dependent specification of olfactory sensory neurons is required for successful integration of olfactory, vomeronasal, and GnRH neurons
2012 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 26, no 8, p. 3464-3472Article in journal (Refereed) Published
Abstract [en]

Inactivation of the LIM-homeodomain 2 gene (Lhx2) results in a severe defect in specification of olfactory sensory neurons (OSNs). However, the ramifications of lack of Lhx2-dependent OSN specification for formation of the primary olfactory pathway have not been addressed, since mutant mice die in utero. We have analyzed prenatal and postnatal consequences of conditionally inactivating Lhx2 selectively in OSNs. A cell-autonomous effect is that OSN axons cannot innervate their target, the olfactory bulb. Moreover, the lack of Lhx2 in OSNs causes unpredicted, non-cell-autonomous phenotypes. First, the olfactory bulb shows pronounced hypoplasia in adults, and the data suggest that innervation by correctly specified OSNs is necessary for adult bulb size and organization. Second, absence of an olfactory nerve in the conditional mutant reveals that the vomeronasal nerve is dependent on olfactory nerve formation. Third, the lack of a proper vomeronasal nerve prevents migration of gonadotropin-releasing hormone (GnRH) cells the whole distance to their final positions in the hypothalamus during embryo development. As adults, the conditional mutants do not pass puberty, and these findings support the view of an exclusive nasal origin of GnRH neurons in the mouse. Thus, Lhx2 in OSNs is required for functional development of three separate systems.—Berghard, A., Hägglund, A.-C., Bohm, S., and Carlsson, L. Lhx2-dependent specification of olfactory sensory neurons is required for successful integration of olfactory, vomeronasal, and GnRH neurons.

Place, publisher, year, edition, pages
Federation of American Society of Experimental Biology (FASEB), 2012
Keywords
mouse embryo development, gonadotropin-releasing hormone neurons, puberty phenotype
National Category
Neurosciences Developmental Biology
Identifiers
urn:nbn:se:umu:diva-55206 (URN)10.1096/fj.12-206193 (DOI)
Funder
Swedish Research Council
Available from: 2012-05-13 Created: 2012-05-13 Last updated: 2018-06-08Bibliographically approved
Öztokatli, H., Hörnberg, M., Berghard, A. & Bohm, S. (2012). Retinoic acid receptor and CNGA2 channel signaling are part of a regulatory feedback loop controlling axonal convergence and survival of olfactory sensory neurons. The FASEB Journal, 26(2), 617-627
Open this publication in new window or tab >>Retinoic acid receptor and CNGA2 channel signaling are part of a regulatory feedback loop controlling axonal convergence and survival of olfactory sensory neurons
2012 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 26, no 2, p. 617-627Article in journal (Refereed) Published
Abstract [en]

Little is known about the identities and functions of extracellular signaling molecules that work in concert with neuronal activity to regulate refinement and maintenance of the mouse olfactory sensory map. We show that expression of a dominant negative retinoic acid receptor (RAR) in olfactory sensory neurons (OSNs) increased the number of glomeruli that incorrectly contained OSN axons expressing different odorant receptors. This phenotype became apparent postnatally, coincided with increased cell death, and was preceded by increased Neuropilin-1 and reduced Kirrel-2 expressions. Kirrel-2-mediated cell adhesion influences odorant receptor-specific axonal convergence and is regulated by odorant receptor signaling via the olfactory cyclic nucleotide-gated (CNG) ion channel. Accordingly, we found that inhibited RAR function correlated with reduced CNG channel expression. Naris occlusion experiments and analysis of CNG channel-deficient mice further indicated that RAR-regulated CNG channel levels influenced the intrinsic neuronal activity required for cell survival in the absence of odor stimulation. Finally, we showed that CNG channel activity regulated expression of the retinoic acid-degrading enzyme Cyp26B1. Combined, these results identify a novel homeostatic feedback mechanism involving retinoic acid metabolism and CNG channel activity, which influences glomerular homogeneity and maintenance of precisely connected OSNs.

Place, publisher, year, edition, pages
Federation of American Society of Experimental Biology (FASEB), 2012
Keywords
retinoids, neuronal activity, caspase-3, Kirrel-2, Neuropilin-1
National Category
Cell and Molecular Biology
Research subject
Medicine
Identifiers
urn:nbn:se:umu:diva-55746 (URN)10.1096/fj.11-192450 (DOI)000300485700015 ()22009938 (PubMedID)
Available from: 2012-05-29 Created: 2012-05-29 Last updated: 2018-06-08Bibliographically approved
Vedin, V., Eriksson, B. & Berghard, A. (2010). Organization of the chemosensory neuroepithelium of the vomeronasal organ of the Scandinavian moose Alces alces. Brain Research, 1306, 53-61
Open this publication in new window or tab >>Organization of the chemosensory neuroepithelium of the vomeronasal organ of the Scandinavian moose Alces alces
2010 (English)In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1306, p. 53-61Article in journal (Refereed) Published
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.

Keywords
Vomeronasal organ, Moose, Alces alces, Accessory olfactory system, Immunohistochemistry, Chemical sense, accessory olfactory-bulb pheromonal communication primates system receptors evolution mammals mouse transduction behavior
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-43203 (URN)10.1016/j.brainres.2009.10.012 (DOI)000272934400006 ()
Funder
Swedish Research CouncilFormas, 221-2006-419
Available from: 2011-04-22 Created: 2011-04-22 Last updated: 2018-06-08Bibliographically approved
Suska, A., Ibáñez, A. B., Lundström, I. & Berghard, A. (2009). G protein-coupled receptor mediated trimethylamine sensing. Biosensors & bioelectronics, 25(4), 715-720
Open this publication in new window or tab >>G protein-coupled receptor mediated trimethylamine sensing
2009 (English)In: Biosensors & bioelectronics, ISSN 0956-5663, E-ISSN 1873-4235, Vol. 25, no 4, p. 715-720Article in journal (Refereed) Published
Abstract [en]

A new approach for the detection of trimethylamine (TMA) using a recombinant cell line of Xenopus laevis melanophores was developed. The cells were genetically modified to express the mouse trace amine-associated receptor 5 (mTAAR5), a G protein-coupled receptor from the mouse olfactory epithelium, which conferred high sensitivity to TMA. Cellular responses to TMA were analyzed by two different techniques, either by absorbance measurements using a microplate reader or by cellular imaging via an inverted microscope. A focused chemical screen allowed the discovery of additional, previously unknown stimuli of mTAAR5. The developed cell-based sensor demonstrated no sensitivity to trimethylamine N-oxide (TMAO), making it suitable for a straightforward evaluation of TMA levels in fish tissue extracts. For the detection of TMA vapor, the cells were covered with agarose, which allowed for intact cell viability for at least 6 h in air. The developed gas measurement platform was able to detect TMA from 1 to 100 ppm within 35 min.

Keywords
cell-based sensor, trace amine-associated receptor, TAAR5, trimethylamine detection, xenopus laevis melanophores
Identifiers
urn:nbn:se:umu:diva-43987 (URN)10.1016/j.bios.2009.08.012 (DOI)19734032 (PubMedID)
Available from: 2011-05-17 Created: 2011-05-17 Last updated: 2018-06-08Bibliographically approved
Vedin, V., Molander, M., Bohm, S. & Berghard, A. (2009). Regional differences in olfactory epithelial homeostasis in the adult mouse. Journal of Comparative Neurology, 513(4), 375-384
Open this publication in new window or tab >>Regional differences in olfactory epithelial homeostasis in the adult mouse
2009 (English)In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 513, no 4, p. 375-384Article in journal (Refereed) Published
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.

Keywords
olfaction, neurogenesis, proliferation, zone, postnatal
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-32741 (URN)10.1002/cne.21973 (DOI)19177519 (PubMedID)
Available from: 2010-03-23 Created: 2010-03-23 Last updated: 2018-06-08Bibliographically approved
Hörnberg, M., Gussing, F., Berghard, A. & Bohm, S. (2009). Retinoic acid selectively inhibits death of basal vomeronasal neurons during late stage of neural circuit formation. Journal of Neurochemistry, 110(4), 1263-1275
Open this publication in new window or tab >>Retinoic acid selectively inhibits death of basal vomeronasal neurons during late stage of neural circuit formation
2009 (English)In: Journal of Neurochemistry, ISSN 0022-3042, E-ISSN 1471-4159, Vol. 110, no 4, p. 1263-1275Article in journal (Refereed) Published
Abstract [en]

In mouse, sexual, aggressive, and social behaviors are influenced by G protein-coupled vomeronasal receptor signaling in two distinct subsets of vomeronasal sensory neurons (VSNs): apical and basal VSNs. In addition, G protein-signaling by these receptors inhibits developmental death of VSNs. We show that cells of the vomeronasal nerve express the retinoic acid (RA) synthesizing enzyme retinal dehydrogenase 2. Analyses of transgenic mice with VSNs expressing a dominant-negative RA receptor indicate that basal VSNs differ from apical VSNs with regard to a transient wave of RA-regulated and caspase 3-mediated cell death during the first postnatal week. Analyses of G-protein subunit deficient mice indicate that RA and vomeronasal receptor signaling combine to regulate postnatal expression of Kirrel-2 (Kin of IRRE-like), a cell adhesion molecule regulating neural activity-dependent formation of precise axonal projections in the main olfactory system. Collectively, the results indicate a novel connection between pre-synaptic RA receptor signaling and neural activity-dependent events that together regulate neuronal survival and maintenance of synaptic contacts.

Keywords
caspase, cell survival, Kirrel, olfactory, retinoic acid, vomeronasal
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-32707 (URN)10.1111/j.1471-4159.2009.06216.x (DOI)000268221500012 ()19519663 (PubMedID)
Funder
Swedish Research Council Formas, K2008-63X-20726-01-3
Available from: 2010-03-23 Created: 2010-03-23 Last updated: 2019-01-24Bibliographically approved
Hägglund, M., Berghard, A., Strotmann, J. & Bohm, S. (2006). Retinoic acid receptor-dependent survival of olfactory sensory neurons in postnatal and adult mice.. Journal of Neuroscience, 26(12), 3281-3291
Open this publication in new window or tab >>Retinoic acid receptor-dependent survival of olfactory sensory neurons in postnatal and adult mice.
2006 (English)In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 26, no 12, p. 3281-3291Article in journal (Refereed) Published
Identifiers
urn:nbn:se:umu:diva-16510 (URN)10.1523/JNEUROSCI.4955-05.2006 (DOI)16554478 (PubMedID)
Available from: 2007-10-04 Created: 2007-10-04 Last updated: 2018-06-09
Norlin, M., Vedin, V., Bohm, S. & Berghard, A. (2005). Odorant-dependent, spatially restricted induction of c-fos in the olfactory epithelium of the mouse.. Journal of Neurochemistry, 96(6), 1594-602
Open this publication in new window or tab >>Odorant-dependent, spatially restricted induction of c-fos in the olfactory epithelium of the mouse.
2005 (English)In: Journal of Neurochemistry, ISSN 0022-3042, E-ISSN 1471-4159, Vol. 96, no 6, p. 1594-602Article 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.

National Category
Cell Biology
Identifiers
urn:nbn:se:umu:diva-16531 (URN)10.1111/j.1471-4159.2005.03159.x (DOI)15935076 (PubMedID)
Available from: 2007-10-05 Created: 2007-10-05 Last updated: 2018-06-09
Organisations

Search in DiVA

Show all publications