Molecular Neuroscience

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Disorders of the central nervous system, such as cerebrovascular diseases, cerebrospinal trauma, and encephalomyelitis, often cause spatiotemporal changes in the nervous system and in various biological systems, such as the immune system and vascular system. We have analyzed disorders of the neural networks in the central nervous system and the subsequent restoration process from the perspective of the functional network of biological systems (Fig. 1 and 2). Further, we have analyzed the mechanism by which the spatiotemporal dynamics in those biological systems control a series of processes. Particularly, the ultimate goal of this study is to elucidate the control mechanism exerted by the associations among the nervous system, immune system, and vascular system. Additionally, we aim to elucidate the principles involved in the operation of living organisms with neural network disorders within the central nervous system by observing such disorders and their functional recovery process with respect to the dynamics of the entire biological system and by conducting a comprehensive analysis of the association between each system. We perceive the central nervous system as a single organ within a biological system; further, studies from the perspective of the involvement of the entire biological system in disorders and recovery of neural networks are scarce. By perceiving disorders in the neural networks and the biological reactions during the subsequent recovery process as a “scrap-and-build” strategy, we aim to elucidate the mechanisms behind a series of reactions as well as their significance that may potentially create a new and never-seen-before trend in Life Sciences.

Figifure 1

Figifure 2

Principal Investigator

Toshihide Yamashita Professor

Research field: Molecular Mechanisms Regulating the Regeneration and Plasticity of Injured Central Nervous System
+81-6-6879-3971
yokada atmark sg.med.osaka-u.ac.jp
Education history

1994.4 – 1996.4 Graduate Student, Graduate School of Medicine, Osaka University (withdrawn from a graduate course to become a Research Associate in Osaka University)
1990.3 Graduated from Osaka University Medical School

Degrees and Licenses

1997 Ph.D. (Osaka University)
1990 M.D. (Osaka University)
1990~ Medical License

Research and career history

2017–present Osaka University Distinguished Professor
2017–present WPI Immunology Frontier Research Center, Osaka University (adjunct)
2009.4–present Professor, Department of Molecular Neuroscience, Grad. Sch. Front. Biosci., Osaka University (adjunct)
2007.12–present Professor, Department of Molecular Neuroscience, Grad. Sch. Med., Osaka University
2003.11–2007.11 Professor and Head, Department of Neurobiology, Grad. Sch. Med., Chiba University
2001.2 – 2003.10 Associate Professor, Department of Anatomy and Neuroscience, Grad. Sch. Med., Osaka University
1998.7 – 2000.9 Research Fellow, Department of Neurobiochemistry, Max-Planck Institute of Neurobiology
1997.11 – 2001.1 Assistant Professor, Department of Anatomy and Neuroscience, Grad. Sch. Med., Osaka University
1996.5 – 1997.10 Research Associate, Department of Molecular Brain System, Grad. Sch. Med., Osaka University
1993.7 – 1994.3 Medical staff in Department of Neurosurgery, Minoh City Hospital
1992.7 – 1993.6 Medical staff in Department of Neurosurgery, Wakakusa Daiichi Hospital
1991.12 – 1992.6 Medical staff in Department of Psychiatry, Asakayama Hospital
1991.5 – 1991.11 Internship in Department of Neurosurgery, Osaka University Hospital
1990.6 – 1991.5 Internship in Department of Neurosurgery, Osaka Koseinenkin Hospital

Members

Rieko Muramatsu Associate Professor
muramatsu atmark molneu.med.osaka-u.ac.jp
Fumitaka Kimura Associate Professor
fkimura atmark molneu.med.osaka-u.ac.jp
Yuki Fujita Assistant Professor
yuki-fujita atmark molneu.med.osaka-u.ac.jp
Mariko Nishibe Specially Appointed Associate Professor
mnishibe atmark molneu.med.osaka-u.ac.jp
Syogo Tanabe Specially Appointed Associate Professor
s-tanabe atmark molneu.med.osaka-u.ac.jp
Ken Matoba Specially Appointed Associate Professor
matoba atmark molneu.med.osaka-u.ac.jp
Hiroshi Tsujioka Specially Appointed Associate Professor
tsujioka atmark molneu.med.osaka-u.ac.jp
Maki Hoshiko JSPS Research Fellow
maki.hoshiko atmark molneu.med.osaka-u.ac.jp
 
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Publications

Fujita, Y., Masuda, K., Nakato, R., Katou, Y., Tanaka, T., Nakayama, M., Takao, K., Miyakawa, T., Shirahige, K. and Yamashita, T. (2017) Cohesin regulates formation of neuronal networks in the brain. J. Exp. Med. 214, 1431-1452.
Fujitani, M., Zhang, S., Fujiki, R., Fujihara, Y. and Yamashita, T. (2017) A chromosome 16p13.11 microduplication causes hyperactivity through dysregulation of miR-484/protocadherin-19 signaling. Mol. Psychiatry 22, 364-374.
Siebold, C., Yamashita, T., Monnier, P., Mueller, B.K. and Pasterkamp, R.J. (2017) RGMs: Structural Insights, Molecular Regulation and Downstream Signaling. Trends Cell Biol. 27, 365-378.
Hayano, Y., Takasu, K., Koyama, Y., Ogawa, K., Minami, K., Asaki, T., Kitada, K., Kuwabara, S. and Yamashita, T. (2016) Dorsal horn interneuron-derived Netrin-4 contributes to spinal sensitization in chronic pain via Unc5B. J. Exp. Med. 213, 2949-2966
van Erp, S., van den Heuvel, D.M.A., Fujita, Y., Robinson, R.A., Hellemons, A.J., Adolfs, Y., Van Battum, E.Y., Blokhuis, A.M., Kuijpers, M., Demmers, J., Hedman, H., Hoogenraad, C.C., Siebold, C., Yamashita, T. and Pasterkamp, R.J. (2015) Lrig2 negatively regulates ectodomain shedding of axon guidance receptors by ADAM proteases. Dev. Cell 35, 537-552..
Arima, Y., Kamimura, D., Yamada, M., Sabharwal, L., Harada, M., Kawamoto, T., Yamashita, T. Ogura, H., Hirano, T. and Murakami, M. (2015) Pain-mediated sympathetic activation induces relapse via microglia accumulation in a multiple sclerosis model. eLife 4, e08733.
Tanabe, S. and Yamashita, T. (2014) Repulsive guidance molecule-a is involved in Th17 cell-induced neurodegeneration in autoimmune encephalomyelitis. Cell Rep. 9, 1459-1470.
Ueno, M., Fujiki, R. and Yamashita, T. (2014) A selector orchestrates cortical function. Nat. Neurosci. 17, 1016-1017.
Hayano, Y., Sasaki, K., Ohmura, N., Takemoto, M., Maeda, Y., Yamashita, T.,Hata, Y., Kitada, K and Yamamoto, N. (2014) Netrin-4 regulates thalamocortical axon branching in an activity-dependent fashion. Proc. Natl. Acad. Sci. USA 111, 15226-15231.
Ueno, M. and Yamashita, T. (2014) Bidirectional tuning of microglia in the developing brain: From neurogenesis to neural circuit formation. Curr. Opin. Neurobiol. 27C, 8-15.
Ueno, M., Fujita, Y., Tanaka, T., Nakamura, Y., Kikuta, J., Ishii, M. and Yamashita, T. (2013) Layer V cortical neurons require microglial support for survival during postnatal development. Nat. Neurosci. 16, 543-551.
Muramatsu, R., Takahashi, C., Miyake, S., Fujimura, H., Mochizuki, H. and Yamashita, T. (2012) Angiogenesis induced by CNS inflammation promotes neural remodeling through vessel-derived prostacyclin. Nature Medicine 18, 1658-1664.
Ueno, M., Hayano, Y., Nakagawa, H. and Yamashita, T. (2012) Intraspinal rewiring of the corticospinal tract requires target-derived brain-derived neurotrophic factor and compensates lost function after brain injury. Brain 135, 1253-1267.
Muramatsu, R., Kubo, T., Mori, M., Nakamura, Y., Fujita, Y., Akutsu, T., Okuno, T., Taniguchi, J., Kumanogoh, A., Yoshida, M., Mochizuki, H., Kuwabara, S. and Yamashita, T. (2011) RGMa modulates T cell responses and is involved in autoimmune encephalomyelitis. Nature Medicine 17, 488-494.
Fujita, Y., Endo, S., Takai, T. and Yamashita, T. (2011) Myelin suppresses axon regeneration by PIR-B/SHP-mediated inhibition of Trk activity. EMBO J. 30, 1389-1401.
Sanuki, R., Onishi, A., Koike, C., Muramatsu, R., Watanabe, S., Muranishi, Y, Irie, S., Ueno, S., Koyasu, T., Matsui, R., Cherasse, Y., Urade, Y., Watanabe, D., Kondo, M., Yamashita, T. and Furukawa, T. (2011) miR-124a is required for hippocampal axogenesis and retinal cone survival through Lhx2 suppression. Nat. Neurosci. 14, 1125–1134
Yamagishi, S., Hampe1, F., Hata, K., del Toro, D., Schwark, M., Kvachnina, E., Bastmeyer, M., Yamashita, T., Tarabykin, V., Klein, R. and Egea. J. (2011) FLRT2 and FLRT3 act as repulsive guidance cues for Unc5-positive neurons. EMBO J. 30, 2920-2933.
Hata, K., Kaibuchi, K., Inagaki, S. and Yamashita, T. (2009) Unc5B associates with LARG to mediate the action of repulsive guidance molecule. J. Cell Biol. 184, 737-750.
Hata, K., Fujitani, M., Yasuda, Y., Doya, H., Saito, T., Yamagishi, S., Mueller, B.K. and Yamashita, T. (2006) RGMa inhibition promotes axonal growth and recovery after spinal cord injury. J. Cell Biol. 173, 47-58.
Yamashita, T. & Tohyama, M. (2003) The p75 receptor acts as a displacement factor that releases Rho from Rho GDI. Nature Neurosci. 6, 461-467.
Higuchi, H., Yamashita, T., Yoshikawa, H. & Tohyama, M. (2003) PKA phosphorylates the p75 receptor and regulates its localization to lipid rafts. EMBO J. 22, 1790-1800.
Yamashita, T., Higuchi, H., and Tohyama, M. (2002) The p75 receptor transduces the signal from myelin-associated glycoprotein to Rho. J. Cell Biol. 157, 565-570
Tanaka, H., Yamashita, T., Asada, M., Mizutani, S., Yoshikawa, H. & Tohyama, M. (2002) Cytoplasmic p21Cip1/WAF1 regulates neurite remodeling by inhibiting Rho-kinase activity. J. Cell Biol. 158, 321-329.
Yamashita, T., Tucker, K. L. & Barde, Y.A. (1999) Neurotrophin binding to the p75 receptor modulates Rho activity and axonal outgrowth. Neuron 24, 585-593..

Awards

2005 Ameritec Prize (USA)
2010 Japan Society for the Promotion of Science Prize (Japan)
2011 Osaka Science Prize (Japan)
2014 Commendation for Science and Technology by the Minister of Education, Culture, Sports, Science and Technology