title: Oncogenic Lmo3 cooperates with Hen2 to induce hydrocephalus in mice.
abstract: We previously reported that LMO3 and HEN2 act as oncogenes in neuroblastoma development through up-regulating MASH1 transcription by interfering with HES1. To confirm these results in vivo, we generated transgenic mice of these genes. Lmo3 or Hen2 was expressed under the control of Wnt1 promoter, which is expressed in the central nervous system and neural crest of the sympathoadrenal lineage from which neuroblastoma develops. Heterozygous Lmo3 and Hen2 transgenic mice (Tg (Lmo3) and Tg (Hen2)) developed hydrocephalus at higher frequency than for the wild type mice, and all heterozygous double-transgenic mice (Tg (Lmo3; Hen2)) developed hydrocephalus. Therefore, Lmo3 and Hen2 may be involved in and have synergistic effects on hydrocephalus development. Although aqueduct stenosis occurred in all genotypes, it was mild in Tg (Lmo3; Hen2) mice. Furthermore, hydrocephalus was detected at E18.5 in Tg (Lmo3; Hen2). These results suggest that the causes of hydrocephalus are not only aqueduct stenosis but also disorder of neocortical development. A similar phenotype was reported in Robo1/2(-/-) mice, in which Hes1 expression level was decreased in ventricular zone progenitors. Thus, it is suggested that the expression levels of Lmo3 and/or Hen2 could determine the fate of stem cells by inhibiting Hes1 function during nervous system development and might be a trigger of aberrant neurogenesis in vivo.
authors.affiliation: Division of Experimental Animal Research, Chiba Cancer Center Research Institute, 666-2 Nitonacho, Chuouku, Chiba 260-8717, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Isogai
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Okumura
authors.forename: Megumi
authors.initials: M
authors.lastname: Saito
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yoshizawa
authors.forename: Kyoko
authors.initials: K
authors.lastname: Itoh
authors.forename: So
authors.initials: S
authors.lastname: Tando
authors.forename: Miki
authors.initials: M
authors.lastname: Ohira
authors.forename: Seiki
authors.initials: S
authors.lastname: Haraguchi
authors.forename: Akira
authors.initials: A
authors.lastname: Nakagawara
authors.forename: Shinji
authors.initials: S
authors.lastname: Fushiki
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nagase
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Wakabayashi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D004843:Epistasis, Genetic; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics; D006849:Hydrocephalus / Q000235:genetics*; D060588:LIM Domain Proteins / Q000235:genetics*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019579:Neocortex / Q000254:growth & development; D058953:Neural Stem Cells / Q000166:cytology; D055495:Neurogenesis / Q000235:genetics; D011401:Promoter Regions, Genetic; D000072056:Transcription Factor HES-1; D051155:Wnt1 Protein / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D000072056:Transcription Factor HES-1; D051155:Wnt1 Protein; C489734:Hes1 protein, mouse; C502335:LMO3 protein, human; C484104:Nhlh2 protein, mouse; C495246:Wnt1 protein, mouse