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Integrated Biology Laboratories

KOKORO-Biology Group

Prof. YAGI Takeshi Prof. YAGI Takeshi

Keywords:

Neuron, Neural network, Synapse formation, Mind, Gene

Understanding the biological bases for generating the mind in the brain

Our investigations are aimed toward understanding the biological bases for generating brain function including memory, mind and consciousness. The brain is a complex multicellular system involving enormous numbers of neurons. The neuron is the basic functional unit of the brain, and neurons are organized by complex networks with many other neurons. We found genetic bases for neuronal individuality in the brain. The extensive molecular diversity of neuronal cell-surface proteins affects neurons' individual properties and connectivity. We are approaching the molecular bases for neuronal individuality and appropriate neuronal wiring during brain development.

Clustered protocadherins are diverse cell-adhesion molecules expressed in the brain. Random and different combinatorial sets of them express in individual neurons, and have roles for generating the complex neural networks and functional neuronal groups (cell assembly) in the brain.

Members

Takeshi Yagi (Professor) yagi[at]fbs.osaka-u.ac.jp
Ryosuke Kaneko (Associate Professor) rkaneko[at]fbs.osaka-u.ac.jp
Noriyuki Sugo (Special Appointed Assistant Professor) sugo[at]fbs.osaka-u.ac.jp
Hiroaki Kobayashi (Assistant Professor) hirokob[at]fbs.osaka-u.ac.jp
Etsuko Tarusawa (Assistant Professor) tarusawa[at]fbs.osaka-u.ac.jp
Mayumi Higuchi (Technical Staff) mhiguchi[at]fbs.osaka-u.ac.jp
Ayako Nishimori (Secretary) a.nishimori[at]fbs.osaka-u.ac.jp
Tomoko Miyashita (Secretary) t.miyashita[at]fbs.osaka-u.ac.jp

You could probably reach more information of individual researchers by Research Map and researcher's search of Osaka-U.

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Q&A

What is your hot research topic?
We focus to reveal mechanisms of clustered protocadherins for combinatorial stcastic expression and neural network formation in individual neurons.
What is your breakthrough or research progress in the last 5 years?
  1. Clonal neurons from same neural stem cells in the cortex build reciprocal connections.
  2. Stochastic expression of clustered protocadherins in individual neurons is determined by epigenetic regulations.
  3. Clustered protocadherins have crucial roles for functional neural network formation.
  4. Clustered protocadherins are correlated with human psyatric disorders.
What kind of background do your lab members have?
Our laboratory members firstly have specialists for molecular biology, developmental technology, electrophysiology, behavior sciences, and psychiatry.
Do you collaborate with institutions outside of Osaka Univ.?
We are collaborated with Icahn School of Medicine at Mount Sinai, Institute for Physiology, RIKEN, University of Tokyo, Kyoto University, Kobe University, Nagoya University, Toyama University, etc.
What kind of careers do your Lab's alumni go on to?
Scientists of University, Institute and pharmaceutical company.
How do you develop your research?
We aim to reveal molecular mechanisms for building complex neural networks of cell assembly based on brain function.

Research Highlights

Publications (Research Articles, Reviews, Books)

2020

Asai H, Ohkawa N, Saitoh Y, Ghandour K, Murayama E, Nishizono H, Matsuo M, Hirayama T, Kaneko R, Muramatsu S, Yagi T, Inokuchi K

Pcdhb deficiency affects hippocampal CA1 ensemble activity and contextual fear discrimination

Mol. Brain 13(1):7  2020 PMID:31959219 DOI:10.1186/s13041-020-0547-z

2019

Picketts DJ, Alvarez-Saavedra M, Yan K, Chaudary N, Hashem LE, Yang D, Repentigny YD, Ioshikhes I, Kothary R, Hirayama T, Yagi T

Snf2h drives chromatin remodeling to prime upper layer cortical neuron development

Front. Molec. Neurosci. 0.66875  2019 PMID:31680852 DOI:10.3389/fnmol.2019.00243

Gu Z, Ueno M, Klinefelter K, Mamidi M, Yagi T, Yoshida Y

Skilled movements require inhibition of corticospinal axon collateral formation in the spinal cord by semaphorin signaling in mice

J. Neurosci. 39(45):8885-8899  2019 PMID:31537704 DOI:10.1523/JNEUROSCI.2832-18.2019

Kozuka T, Omori Y, Watanabe S, Tarusawa E, Yamamoto H, Chaya T, Furuhashi M, Morita M, Sato T, Hirose S, Ohkawa Y, Yoshimura Y, Hikida T, Furukawa T

miR-124 dosage regulates prefrontal cortex function by dopaminergic modulation.

Sci Rep 9(1):3445  2019 PMID:30837489 DOI:10.1038/s41598-019-38910-2

Shao Z, Noh H, Kim WB, Ni P, Nguyen C, Cote SE, Noyes E, Zhao J, Parsons T, Park JM, Zheng K, Park JJ, Coyle JT, Weinberger DR, Straub RE, Berman KF, Apud J, Ongur D, Cohen BM, McPhie DL, Rapoport JL, Perlis RH, Lanz TA, Xi S, Yin C, Huang W, Hirayama T, Fukuda E, Yagi T, Ghosh S, Eggan KC, Kim HY, Eisenberg LM, Moghadam A, Stanton P, Cho J-H and Chung S

Dysregulated protocadherin-pathway activity as an intrinsic defect in iPSC-derived cortical interneurons from patients with schizophrenia.

Nat. Neurosci. 22(2):229-242  2019 PMID:30664768 DOI:10.1038/s41593-018-0313-z

2018

Yamagishi T, Yoshitake K, Kamatani D,Watanabe K, Tsukano H, Hishida R, Takahashi K, Takahashi S, Horii A, Yagi T, Shibuki K

Molecular diversity of clustered protocadherin-a required for sensory integration and short-term memory in mice.

Sci Rep 8(1):9616  2018 PMID:29941942 DOI:10.1038/s41598-018-28034-4

2017

Katori S, Noguchi Y, Okayama A, Kawamura Y, Leo W, Sakimura K, Hirabayashi T, Iwasato T, Yagi T

Protocadherin-αC2 is required for diffuse projections of serotonergic axons.

Sci Rep 7:15908  2017 PMID:29162883 DOI:10.1038/s41598-017-16120-y

Atucha E, Karew A, Kitsukawa T, Sauvage MM

Recognition memory: Cellular evidence of a massive contribution of the LEC to familiarity and a lack of involvement of the hippocampal subfields CA1and CA3

Hippocampus 27(10):1083-1092  2017 PMID:28667695 DOI:10.1002/hipo.22754

Onishi K, Uyeda A, Shida M, Hirayama T, Yagi T, Yamamoto N, Sugo N

Genome Stability by DNA polymerase β in Neural Progenitors Contributes to Neuronal Differentiation in Cortical Development.

J. Neurosci. 37(35):8444-8458  2017 PMID:28765330 DOI:10.1523/JNEUROSCI.0665-17

Jiang Y, Loh YE, Rajarajan P, Hirayama T, Liao W, Kassim BS, Javidfar B, Hartley BJ, Kleofas L, Park RB, Labonte B, Ho SM, Chandrasekaran S, Do C, Ramirez BR, Peter CJ, C W JT, Safaie BM, Morishita H, Roussos P, Nestler EJ, Schaefer A, Tycko B, Brennand KJ, Yagi T, Shen L and Akbarian S

The methyltransferase SETDB1 regulates a large neuron- specific topological chromatin domain.

Nature Genet. 49(8):1239-1250  2017 PMID:28671686 DOI:10.1038/ng.3906

Nakamura F, Okada T, Shishikura M, Uetani N, Taniguchi M, Yagi T, Iwakura Y, Ohshima T, Goshima Y, Strittmatter S

Protein Tyrosine Phosphatase δ mediates the Sema3A-induced cortical basal dendritic arborization through the activation of Fyn tyrosine kinase.

J. Neurosci. 37(30):7125-7139  2017 PMID:28637841 DOI:10.1523/JNEUROSCI.2519-16

Hirayama T, Yagi T

Regulation of clustered protocadherin genes in individual neurons.

Front. Molec. Neurosci. 69:122-130  2017 PMID:28591566 DOI:10.1016/j.semcdb

Tatsumi R, Suzuki T, Do M-K Q, Ohya Y, Anderson JE, Shibata A, Kawaguchi M, Ohya S, Ohtsubo H, Mizunoya W, Sawano S, Komiya Y, Ichitsubo R, Ojima K, Nishimatsu S, Nohno T, Ohsawa Y, Sunada Y, Nakamura M, Furuse M, Ikeuchi Y, Nishimura T, Yagi T, Allen RE

Slow-Myofiber Commitment by Semaphorin 3A Secreted from Myogenic Stem Cells.

Stem Cells 35(7):1815-1834  2017 PMID:28480592 DOI:10.1002/stem.2639

Hasegawa S, Kobayashi H, Kumagai M, Nishimaru H, Tarusawa E, Kanda H, Sanbo M, Yoshimura Y, Hirabayashi M, Hirabayashi T, Yagi T

Clustered protocadherins are required for building functional neural circuits

Front. Molec. Neurosci. 0.495833333  2017 PMID:28484370 DOI:10.3389/fnmol.2017.00114

Nakamura T, Nagata M, Yagi T, Graybiel AM, Yamamori T, Kitsukawa T

Learning new sequential stepping patterns requires striatal plasticity during the earliest phase of acquisition.

Eur. J. Neurosci. 45(7):901-911  2017 PMID:28177160 DOI:10.1111/ejn.13537

2016

Hasegawa S, Kumagai M, Hagihara M, Nishimaru H, Hirano K, Kaneko R, Okayama A, Hirayama T, Sanbo M, Hirabayashi M, Watanabe M, Hirabayashi T, Yagi T

Distinct and cooperative functions for the protocadherin-α, -β and -γ clusters in neuronal survival and axon targeting.

Front. Molec. Neurosci. 0.482638889  2016 PMID:28066179 DOI:10.3389/fnmol.2016.00155

Tarusawa E, Sanbo M, Okayama A, Miyashita T, Kitsukawa T, Hirayama T, Hirabayashi T, Hasegawa S, Kaneko R, Toyoda S, Kobayashi T, Kato-Itoh M, Nakauchi H, Hirabayashi M, Yagi T, Yoshimura Y

Establishment of high reciprocal connectivity between clonal cortical neurons is regulated by the Dnmt3b DNA methyltransferase and clustered protocadherins.

BMC Biol. 14(1):103  2016 PMID:27912755 DOI:10.1186/s12915-016-0326-6

Mochizuki Y, Onaga T, Shimazaki H, Shimokawa T, Tsubo Y, Kimura R, Saiki A, Sakai Y, Isomura Y, Fujisawa S, Shibata K, Hirai D, Furuta T, Kaneko T, Takahashi S, Nakazono T, Ishino S, Sakurai Y, Kitsukawa T, Lee JW, Kee H, Jung MW, Babul C, Maldonado PE, Takahashi K, Arce-McShane FI, Ross CF, Sessle BJ, Hatsopoulos NG, Brochier T, Riehle A, Chorley P, Grun S, Nishijo H, Ichihara-Takeda S, Funahashi S, Shima K, Mushiake H, Yamane Y, Tamura H, Fujita I, Inaba N, Kawano K, Kurkin S, Fukushima K, Kurata K, Taira M, Tsutsui K, Ogawa T, Komatsu H, Koida K, Toyama K, Richmond BJ, Shinomoto S

Similarity in neuronal firing regimes across mammalian species.

J. Neurosci. 36(21):5736-47  2016 PMID:27225764 DOI:10.1523/JNEUROSCI.0230-16.2016

Lux V, Atucha E, Kitsukawa T, Sauvage MM

Imaging a memory trace over half a life-time in the medial temporal lobe reveals a time-limited role of CAA3 neurons in retrieval.

eLife 5:e11862  2016 PMID:26880561 DOI:10.7554/eLife.11862

Kaneko R, Sato A, Hamada S, Yagi T, Ohsawa I, Ohtsuki M, Kobayashi E, Hirabayashi M, Murakami T

Transgenic rat model of childhood-onset dermatitis by overexpressing telomerase reverse transcriptase (TERT).

Transgenic Res. 25(4):413-24  2016 PMID:26885830 DOI:10.1007/s11248-016-9939-3

Our ideal candidate (as a graduate student)

We are looking for a highly motivated person to work on our research topics as our lab member. Our lab welcomes the person who loves taking care of creatures, hand working and handcraft too. Any kind of background (such as your expertise or major) is available.

Contact

KOKORO-Biology Group, Graduate School of Frontier Biosciences, Osaka University,
1-3 Yamadaoka, Suita, Osaka 565-0871 Japan.

TEL: +81-6-6879-7991

E-mail: yagi[at]fbs.osaka-u.ac.jp (Prof. Takeshi Yagi)

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