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Lhx2-dependent specification of olfactory sensory neurons is required for successful integration of olfactory, vomeronasal, and GnRH neurons
Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). (Berghard)
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). (Bohm)
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
2012 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 26, no 8, 3464-3472 p.Article 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. Vol. 26, no 8, 3464-3472 p.
Keyword [en]
mouse embryo development, gonadotropin-releasing hormone neurons, puberty phenotype
National Category
Neurosciences Developmental Biology
Identifiers
URN: urn:nbn:se:umu:diva-55206DOI: 10.1096/fj.12-206193OAI: oai:DiVA.org:umu-55206DiVA: diva2:526485
Funder
Swedish Research Council
Available from: 2012-05-13 Created: 2012-05-13 Last updated: 2017-12-07Bibliographically approved

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Berghard, AnnaHägglund, Anna-CarinBohm, StaffanCarlsson, Leif
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Department of Molecular Biology (Faculty of Science and Technology)Umeå Centre for Molecular Medicine (UCMM)Department of Molecular Biology (Faculty of Medicine)
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NeurosciencesDevelopmental Biology

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