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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, 643-656 p.Article 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, 643-656 p.
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: diva2:732136
Available from: 2014-07-03 Created: 2014-06-03 Last updated: 2017-12-05Bibliographically approved

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