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Disease Mechanism Research Core

Laboratory for Behavioral and Developmental Disorders

Jun ARUGA, M.D., Ph.D.
Jun ARUGA, M.D., Ph.D.
Laboratory Head
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PublicationMain Publications at RIKEN

Research Areas

Vertebrates have a highly organized and centralized nervous system, while the nervous system of invertebrate animals is various, ranging from the diffused nervous system in jellyfish to a moderately centralized nervous system in insects. The diversity of the nervous system is based on the genetic information that has been accumulated and sophisticated in the course of evolution. We perform comparative analysis on the structure, function and expression of genes critically involved in the neurogenesis, such as Zic, Slitrk and Lrfn, as well as other uncharacterized genes expressed in neural tissue. These analyses aim at a comprehensive understanding of the role of the genes and cis-regulatory elements in the appearance of complicated nervous system in animals. As a benefit of the comparative genomic analysis, we are developing and analyzing several model animals for neurodevelopmental disorders.


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Phylogenetic analysis of Zic genes.(Left) Pictures of animals used in the analysis (upper left, Asterina pectinifera; upper right, Nematostella vectensis; middle left, Loligo bleekeri; middle right, Tubifex tubifex; lower left, Artemia franciscana; lower right, Scolionema suvaense). (Right) Hypothetical model that explains the diversity of Zic genes in the Eumetazoa. Thick horizontal bars indicate intron and flanking region. Green indicates protein coding regions without clearly conserved domain structures; red indicates zinc finger domains; dark blue indicates ZOC; purple indicates ZF-NC.

Research Subjects

  1. Studies on the pathogenesis of neurodevelopmental disorders using model animals
  2. Studies on the regulatory mechanism underlying proliferation and differentiation of neuronal progenitors
  3. Phylogenic comparative analysis of genes mediating neurogenesis

Selected Publications

  1. Katayama, K-i., Yamada, K., Ornthanalai, V.G., Inoue, T., Ota, M., Murphy, N.P., and Aruga, J.:
    "Slitrk1-deficient mice display elevated anxiety-like behavior and noradrenergic abnormalities."
    Mol. Psychiatry (published online, 2008)
  2. Hatayama, M., Tomizawa, T., Bouvagnet, P., Kose, S., Imamoto, N., Yokoyama, S., Mikoshiba, K., Kigawa, T., and Aruga, J.:
    "Functional and structural basis of the nuclear localization signalin the ZIC3 zinc finger domain, a role of conserved tryptophan residue in the zinc finger domain."
    Hum. Mol. Genet. 17, 3459-3473. (2008)
  3. Inoue, T., Ogawa, M., Mikoshiba, K., and Aruga, J.:
    "Zic deficiency in the cortical marginal zone and meninges results in cortical lamination defects resembling those in type II lissencephaly."
    J. Neurosci. 28, 4712-4725. (2008)
  4. Takahashi, H., Kamiya, A., Ishiguro, A., Suzuki, A.C., Saitou, N., Toyoda, A., and Aruga, J.:
    "Conservation and diversification of Msx protein in metazoan evolution."
    Mol. Biol. Evol. 25, 69-82. (2008)
  5. Ogawa,　M., Mizugishi, K., Ishiguro, A., Koyabu, Y., Imai, Y., Takahashi, R., Mikoshiba, K., and Aruga, J.:
    "Rines/RNF180, a novel RING finger gene-encoded product, is a membrane-bound ubiquitin ligase."
    Genes Cells 13, 397-409. (2008)
  6. Inoue, T., Ota, M., Ogawa, M., Mikoshiba, K., and Aruga, J.:
    "Zic1 and Zic3 regulate medial forebrain development through expansion of neuronal progenitors."
    J. Neurosci. 27, 5461-5473. (2007)
  7. Inoue, T., Ota, M., Mikoshiba, K., and Aruga, J.:
    "Zic2 and Zic3 synergistically control neurulation and segmentation of paraxial mesoderm in mouse embryo."
    Dev. Biol. 306, 669-684. (2007)
  8. Ishiguro, A., Ideta, M., Mikoshiba, K., Chen, D.J., and Aruga, J.:
    "Zic2-dependent transcriptional regulation is mediated by DNA-dependent protein kinase, poly(ADP-ribose) polymerase and RNA helicase A."
    J. Biol. Chem. 282, 9983-9995. (2007)
  9. Aruga, J., Yoshikawa, F., Nozaki, Y., Sakaki, Y., Toyoda, A., and Furuichi, T.:
    "An oligodendrocyte enhancer in a phylogenetically conserved intron region of the mammalian myelin gene Opalin."
    J. Neurochem. 102, 1533-1547. (2007)
  10. Aruga, J., Odaka, Y.S., Kamiya, A., and Furuya, H.:
    "Dicyema Pax6 and Zic, tool-kit genes in a highly simplified bilaterian."
    BMC Evol. Biol. 7, 201. (2007)

Main Publications at RIKEN


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