title: Progressive effects of N-myc deficiency on proliferation, neurogenesis, and morphogenesis in the olfactory epithelium.
abstract: 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.
authors.affiliation: Umeå Centre for Molecular Medicine, Umeå University, 901 87, Umeå, Sweden.
authors.forename: Walter
authors.initials: W
authors.lastname: Wittmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Schimmang
authors.forename: Lena
authors.initials: L
authors.lastname: Gunhaga
mesh_terms: D000367:Age Factors; D000818:Animals; D049109:Cell Proliferation / Q000235:genetics*; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics*; D009831:Olfactory Mucosa / Q000166:cytology / Q000196:embryology*; D009833:Olfactory Pathways / Q000033:anatomy & histology / Q000201:enzymology; D016271:Proto-Oncogene Proteins c-myc / Q000172:deficiency* / Q000235:genetics; D019147:Vomeronasal Organ / Q000166:cytology / Q000196:embryology
chemical_list: D009419:Nerve Tissue Proteins; D016271:Proto-Oncogene Proteins c-myc; D007987:Gonadotropin-Releasing Hormone
keywords: N-myc; mouse; neurogenesis; olfactory epithelium; vomeronasal organ