Laboratory for Behavioral and Developmental Disorders

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.

Research Subjects

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

Publications

1. M. Tekin, B.A. Chioza, Y. Matsumoto, O. Diaz-Horta, H. E. Cross 4, D. Duman, H. Kokotas, H. L. Moore-Barton, K. Sakoori, M. Ota, Y. S. Odaka, J. Foster II, F.B. Cengiz, S. Tokgoz-Yilmaz, O. Tekeli, M. Grigoriadou, M. B. Petersen, A. Sreekantan-Nair, K. Gurtz, X.-J. Xia, A. Pandya, M. A. Patton, J. I. Young, J. Aruga, A. H. Crosby:
   "SLITRK6 Mutations Cause Myopia and Deafness in Humans and Mice."
   J. Clin. Invest. in press (2013)
2. Takahashi, H., Katayama, K-i., Sohya, K., Miyamoto, H., Prasad, T., Matsumoto, Y., Ota, M., Yasuda, H., Tsumoto, T., Aruga, J., Craig, A.M.:
   "Selective control of inhibitory synapse development by Slitrk3-PTPdelta trans-synaptic interaction."
   Nat. Neurosi. DOI: 10.1038/nn.3040 (2012)
3. Hatayama, M., Ishiguro, A., Iwayama, Y., Takashima, N., Sakoori, K., Toyota, T., Nozaki, Y., Odaka, Y.S., Yamada, K., Yoshikawa, T., Aruga, J.:
   "Zic2 hypomorphic mutant mice as a schizophrenia model and ZIC2 mutations identified in schizophrenia patients."
   Scientific Reports 1:16. (2011)
4. Takashima, N., Odaka, Y.S., Sakoori, K., Akagi, T., Hashikawa, T., Morimura, N., Yamada, K., Aruga, J.:
   "Impaired cognitive function and altered hippocampal synapse morphology in mice lacking Lrrtm1, a gene associated with schizophrenia."
   Plos One 6: e22716. (2011).
5. Matsumoto, Y., Katayama, K., Okamoto, T., Yamada, K., Takashima, N., Nagao, S., Aruga, J.
   "Impaired Auditory-Vestibular Functions and Behavioral Abnormalities of Slitrk6-Deficient Mice"
   PLoS One 6: e16497. (2011)
6. Hatayama, M., Aruga, J.:
   "Characterization of the tandem CWCH2 sequence motif: a hallmark of inter-zinc finger interactions."
   BMC Evol. Biol. 10 e53 (2010)
7. Katayama, K-i., Zine, A., Ota, M., Matsumoto, Y., Inoue, T., Fritzsch, B., Aruga, J.:
   "Disorganized innervation and neuronal loss in the inner ear of Slitrk6-deficient mice"
   PLoS One 4: e7786. (2009)
8. Katayama, K-i, Yamada, K., Ornthanalai, V. G.., Inoue, T., Ota, M., Murphy, N.P., Aruga, J.:
   "Slitrk1-deficient mice display elevated anxiety-like behavior and noradrenergic abnormalities."
   Mol. Psychiatry 15, 177-184. (2010) (published online, 2008)
9. Hatayama, M., Tomizawa, T., Bouvagnet, P., Kose, S., Imamoto, N., Yokoyama, S., Mikoshiba, K., Kigawa, T., 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)
10. Inoue, T., Ogawa, M., Mikoshiba, K., 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)