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Progressive effects of N-myc deficiency on proliferation, neurogenesis, and morphogenesis in the olfactory epithelium
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
Univ Valladolid, Inst Biol & Mol Genet, Valladolid 47003, Spain.
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
2014 (English)In: Developmental Neurobiology, ISSN 1932-8451, E-ISSN 1932-846X, Vol. 74, no 6, p. 643-656Article in journal (Refereed) Published
Abstract [en]

N-myc belongs to the myc proto-oncogene family, which is involved in numerous cellular processes such as proliferation, growth, apoptosis, and differentiation. Conditional deletion of N-myc in the mouse nervous system disrupted brain development, indicating that N-myc plays an essential role during neural development. How the development of the olfactory epithelium and neurogenesis within are affected by the loss of N-myc has, however, not been determined. To address these issues, we examined an N-myc(Foxg1Cre) conditional mouse line, in which N-myc is depleted in the olfactory epithelium. First changes in N-myc mutants were detected at E11.5, with reduced proliferation and neurogenesis in a slightly smaller olfactory epithelium. The phenotype was more pronounced at E13.5, with a complete lack of Hes5-positive progenitor cells, decreased proliferation, and neurogenesis. In addition, stereological analyses revealed reduced cell size of post-mitotic neurons in the olfactory epithelium, which contributed to a smaller olfactory pit. Furthermore, we observed diminished proliferation and neurogenesis also in the vomeronasal organ, which likewise was reduced in size. In addition, the generation of gonadotropin-releasing hormone neurons was severely reduced in N-myc mutants. Thus, diminished neurogenesis and proliferation in combination with smaller neurons might explain the morphological defects in the N-myc depleted olfactory structures. Moreover, our results suggest an important role for N-myc in regulating ongoing neurogenesis, in part by maintaining the Hes5-positive progenitor pool. In summary, our results provide evidence that N-myc deficiency in the olfactory epithelium progressively diminishes proliferation and neurogenesis with negative consequences at structural and cellular levels. 

Place, publisher, year, edition, pages
2014. Vol. 74, no 6, p. 643-656
Keyword [en]
vomeronasal organ, mouse, neurogenesis, olfactory epithelium, N-myc
National Category
Neurology Developmental Biology
Identifiers
URN: urn:nbn:se:umu:diva-89452DOI: 10.1002/dneu.22162ISI: 000335362300007OAI: oai:DiVA.org:umu-89452DiVA, id: diva2:732136
Available from: 2014-07-03 Created: 2014-06-03 Last updated: 2017-12-05Bibliographically approved

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