Tohoku Forum for Creativity Thematic Program 2015

Frontiers of Brain Science

Symposium on

Development and Disease
Abstract

August 24, Mon. ‒ 26, Wed., 2015

Auditorium of the International Center for Smart Aging Research
Seiryo Campus, Tohoku University

Organizers
Yasuyuki Taki

Tomomi Shimogori

Graduate School of Medicine / IDAC, Tohoku University

Riken BSI

General Organizers
Toshio Iijima

Graduate School of Life Sciences, Tohoku University

Noriko Osumi

Graduate School of Medicine, Tohoku University

Contents

Scope

2

Committees

3

Access4

Congress Information

6

Registration

7

Social Programs

8

Time Table

9

Abstracts and Profiles
Principal Speakers

13

Short Talks and Posters

48

1

Scope of the Symposium
All of the information required to generate the intricate design of ourcomplex brains is present in the zygote after fertilization. These genetic andepigenetic

programs

arecarefully

implemented

duringembryonic

development, during which each cell is correctly assigned its location andfunction as the embryo grows. Small alterations in this seemingly impossible
task sometimes occur, and can have profound consequences which may
ultimately result in neurodevelopmental diseases. In the second symposium,
we will discuss how the program of neural development unfolds, with theaim of understanding how errors in these processes can result in thedevelopment of brain disease.

2

Committees
Supported by
Tohoku Forum for Creativity (TFC)
Tohoku University, Institute for Development, Aging & Cancer (IDAC)
Tohoku Brain Science Center (BSC)
Tohoku University Graduate School of Medicine, United Center for Advanced
Research & Translational Medicine (ART)General Organizers
Toshio Iijima (Professor, Graduate School of Life Sciences, Tohoku University)
Noriko Osumi (Professor, Graduate School of Medicine, Tohoku University)

Symposium Organizers
Yasuyuki Taki (Professor, Graduate School of Medicine / IDAC, Tohoku University)
Tomomi Shimogori (Team Leader, Riken BSI)

3

Access
How To Get Seiryo Campus

4Transportation

Seiryo Campus

Seiryo Campus

Smart Ageing International
Research Center5

Congress Information
Date
August 24, 2015 - August 26, 2015

Venue
Auditorium of the International Center for Smart Aging Research

Main Theme
Development and Disease

Official Language
EnglishSmoking
Smoking is forbidden anywhere inside Seiryo Campus and the main building

Filming and Photography
Filming, photography and recording are prohibited. Please refrain from carrying
recording devices into the presentation venue.

Congress website
http://www.tfc.tohoku.ac.jp/event/2443.html

6Registration
Registration Desk
Entrance of the Auditorium on 1st floor in the Smart Aging Research Building, SeiryoCampus.

Open hours
Mon. August 24: 13:00Tue. August 25: 9:10-17:30
Wed. August 26: 9:30-15:50

Registration Fee
Free (Participants who will join the get together party or the reception are requested to
pay the admission fee)7Social programs @ Lobby
Mon. August 24: Get Together party (18:30 - )Tue. August 25: Lunch & Poster (12:10 - ), Reception (17:30 - )Wed. August 26: Lunch & Poster (12:10 - )8Time Table
Mon. August 24
AM

Lab Tour / discussion

13:00

Welcome (Dean, IDAC, Tohoku University)

Session 1: Brain Development
13:10

Francois Guillemot (Institute for Medical Research, UK)
Signals and factors controlling stem cell activity in the adult brain

14:10

Shubha Tole (Tata Institute of Fundamental Research, India)
Early patterning of the cortical primordium

14:50

Short talk 1(1) Takako Kikkawa
Dmrt genes differentially participate in Cajal-Retzius cell
development of the cerebral cortex(2) Dan Ohtan Wang
Imaging RNA in Living Neural Circuits with Hybridizationsensitive Fluorescent Probes
Break

15:20
15:40

Tomomi Shimogori (RIKEN BSI, Japan)
Input from the thalamus creates diversity of the cortical neurons

16:20

Goichi Miyoshi (@Fishell Lab, New York University, USA)
Assembly of neocortical circuitry by FoxG1, a gene associatedwith neurocognitive disorders

16:50

Yusuke Hirabayashi (@Pollex Lab, Columbia University, USA)
Exploring the role of the mitochondria/endoplasmic reticulum(ER) interface in axonal development

18:00

Get together @ Lobby of the same building

9Tue. August 25
Session 2: Brain Evolution
09:10

Wieland Huttner (Max Planck Institute, Dresden, Germany)
Neural stem and progenitor cells and neocortex expansion indevelopment and evolution.

10:10

Short talk 2(1) Takuya Imamura
Gene-activation-associated long non-coding RNAs for
species-dependent epigenome formation(2) Kouta Kanno
Individual differences of courtship ultrasonic vocalizations
and its neuronal correlates in male mice
Break

10:40
11:00

Erich Jarvis (Duke University Medical Center, USA)
Brain evolution of complex behavioral traits: vocal learning andspoken language

11:40

Short talk 3(1) Asuka Matsui
Neural activity dependent BTBD3 translocation to thecytoskeleton is essential for proper dendrite development(2) Carina Hanashima
Neuronal subtype specification in establishing the cerebral
cortex12:25

Lunch & Poster session10Tue. August 25
Session 3: Models for Neurodevelopmental Disease
14:00

Noboru Hiroi (Albert Einstein College of Medicine, USA)
Postnatal neurogenesis and dimensional features of autism in a
genetic mouse model of 22q11.2 copy number variants

14:40

Noriko Osumi (Tohoku University, Japan)
Crosstalk between Pax6 haploinsuffciency and prenatal aging
in modulating offspring behavior: a possible role for epigenetic
modification

15:20

Break

Session 4: Clinical Studies of Neurodevelopmental Disease
15:40

Short talk 4(1) Mikio Hoshino
Analysis of autism susceptibility candidate 2 gene during
development

16:10

Stephan Sanders (UCSF, USA)
Genomic architecture and gene discovery in autism spectrum
disorder16:50

Hidenori Yamasue (Tokyo University, Japan)
Crosstalk between neuroscience and clinical psychiatry withoxytocin in a neurodevelopmental disorder

17:30

Reception@Lobby of the same building

11

Wed. August 26

09:30

Yasuyuki Taki (Tohoku University, Japan)
Brain development using magnetic resonance imaging in healthy
children

10:10

Kenji Tsuchiya (Hamamatsu Medical University, Japan)
Neurodevelopmental Trajectories of Children with Autism
Spectrum Disorder

10:50

Break

11:10

Atsushi Senju (Birkbeck University of London, UK)
Development of spontaneous social cognition and autism

12:00

Lunch & Poster session

13:10

Yoko Kamio (National Center for Neurology and Psychiatry, Japan)
Early detection and early intervention for ASD during life course
development: Not only for social communication problems but
also for diverse mental health issues

13:50

Masahiro Hirai (Jichi Medical University, Japan)
Embodied cognition from inside out in atypical development

14:30

Break

14:50

Paul Matthews (Imperial College, UK)
Imaging in large populations: better defining later life brain
disease risks in terms of development, exposure and aging

15:50

Closing Remarks (TBA)

12Abstracts for
Principal Speakers

13François Guillemot
The Francis Crick Institute, Mill Hill laboratory, London, UK
francois.guillemot@crick.ac.uk【Biographical Sketch】

2015 – presentGroup leader, The Francis Crick Institute, London UK2009 - 2015

Head of the Division of Molecular Neurobiology
National Institute for Medical Research, London UK

2002 - 2009

Programme Leader
National Institute for Medical Research, London UK

2002 - present

Honorary Reader, Department of Anatomy and Developmental
Biology, University College, London UK

1996 - 2002

Research Director, Centre National de la Recherche
Scientifique, IGBMC, Strasbourg, France

1994 - 1996

Research Investigator, Centre National de la Recherche
Scientifique, IGBMC, Strasbourg, France

1991 - 1994

Postdoctoral Fellow, Samuel Lunenfeld Research Institute
Mt Sinai Hospital, Toronto, Canada

1989 - 1991

Postdoctoral Fellow, Department of Genetics
Harvard Medical School, Boston MA, USA

14

Signals and factors controlling stem cell activity in the adult brain
François Guillemot
The Francis Crick Institute, Mill Hill laboratory, London, UK

Neural stem cells can adopt diverse fates, including quiescence, self-renewal and neuronal or glial
differentiation. The selection of appropriate stem cell fates is crucial for the normal growth of theembryonic brain and for the functional integrity of the mature brain.
The control of neural stem cells fates by extracellular signals has been thoroughly investigated. In
contrast, little is known of the transcription factors that mediate the activity of these extrinsic signals
and implement appropriate fate decisions.
Using high throughput genomic analysis and genetic approaches in neural stem cell cultures and in theembryonic and adult mouse brain in vivo, we have identified two transcription factors, ASCL1 and
NFIX, which respectively promote neural stem cell activity and neural stem cell quiescence in theadult brain and in stem cell culture. We are currently investigating the regulation of the activity ofthese factors and the nature of the gene expression programmes that they activate.

15

ShubhaTole
Department of Biological Sciences
Tata Institute of Fundamental Research
Mumbai-400,005, India【Biographical Sketch】

2011- present

Professor, Department of Biological Sciences Tata Institute of Fundamental
Research, India

2014

Visiting Professor, University of Geneva

2008 - 2009

Visiting Associate Professor, Stanford University

2007 - 2011

Associate Professor, Tata Institute of Fundamental Research, India

2002 - 2007

Reader, Tata Institute of Fundamental Research, India

1999 - 2002

Fellow, Tata Institute of Fundamental Research, India

1994 - 1999

Post Doctoral Fellow, University of Chicago

16

Early Patterning of the Cortical Primordium
Shubha Tole,
Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India

The cerebral cortex arises from a simple sheet of neuroepithelial tissue in the embryo. How this sheet
is patterned to produce multiple cortical structures in a reliable and reproducible manner is a questionof both evolution and development. We explored interactions between three regulators of earlypatterning, transcription factors Foxg1, Lhx2, and Pax6. Using combinations of double mutants, we
identified mechanisms that regulate the formation and position of the cortical hem, a signaling center
that is responsible for inducing hippocampal fate in adjacent cortical tissue. These genetic
interactions provide insight into the early steps of patterning of the cortical primordium. Further, wefound that hem is itself part of a forebrain hem system that may have arisen as part of an evolutionary
mechanism to regulate cortical development.

References:
Mangale et al., 2008: Lhx2 selector activity specifies cortical identity and suppresses hippocampal
organizer fate. Science 319: 304-309, 2008
Roy et al., 2013: Lhx2 regulates the development of the forebrain hem system. Cerebral Cortex
10.1093/cercor/bhs421
Work in Dr. Tole’s lab has been supported by a Wellcome Trust Senior Fellowship (056684/Z/99/Z),
Swarnajayanti Fellowship (Dept. of Science and Technology, Govt. of India), and grants from the
Department of Biotechnology, and the Department of Science and Technology, Govt. of India.

17

Tomomi Shimogori
RIKEN Brain Science Institute, Wako, Japantshimogori@brain.riken.jp【Biographical Sketch】

2010 - present

RIKEN BSI Team Leader of Lab for Molecular Mechanisms of Thalamus
Development

2004 – 2010

RIKEN BSI Unit Leader of Shimogori Research Unit

1998 – 2004

Dept. Neurobiology, Pharmacology and Physiology, University of
Chicago, USA Laboratory of Dr. Elizabeth A. Grove18

Input from the thalamus creates diversity of the cortical neuron
Tomomi Shimogori
RIKEN Brain Science Institute, Wako, Japan

Brain development at the embryonic stage is heavily controlled by intrinsic factors. Such as, numberof cells to generate and types of cells to differentiate, are controlled by cues at ventricular/
subventricular zone and at their early postmitotic stages. Axons are guided to their target area andmake connections by guidance cues. However, this blueprint of neuronal circuit development needs
to be modified and rewired at their postnatal stages. This plasticity is important for animal to obtainbetter neuronal circuit that control animals behavior in most efficient way for survival. Meanwhile,
negative factors such as stress in early postnatal stage can also change circuit development whichcauses abnormal behavior later in their adult stages. Therefore, revealing mechanism of experience
dependent brain development is important to understand how we can grow healthy brain or avoid
developing sick brain. In my talk, I would like to discuss about molecular mechanism of experience
dependent neuronal circuit development take place in postnatal brain, especially how cortical neurons
are specified by input coming from thalamus.

References:
Mashiko et al.: Comparative anatomy of marmoset and mouse cortex from genomic expression. J
Neurosci. 32(15):5039-53, 2012
Matsui et al.: BTBD3 controls dendrite orientation toward active axons in mammalian neocortex.
Science 342(6162), 1114-1118, 201319

Goichi Miyoshi
Work Address: 507, 5th Floor, NYU Neuroscience Institute,
Smilow Research Center,
New York University School of Medicine, 522 First Avenue,
New York, NY, 10016【Biographical Sketch】

2004 - present

NYU Neuroscience Institute, Smilow Research Center / Skirball Institute
New York UniversitySchool of Medicine, New York, NY
Postdoctoral fellow, laboratory of Dr. Gordon Fishell

1999 - 2004

Graduate School of Biostudies, Kyoto University
Graduate student, laboratory of Dr. Ryoichiro Kageyama
Ph.D., BiostudyMay 200420

Assembly of neocortical circuitry by FoxG1, a gene associated withneurocognitive disorders
Goichi Miyoshi
NYU Neuroscience Institute, New York University School of Medicine, New York, USA,The mammalian cerebral cortex is composed of a sophisticated neuronal network that processes
higher order information such as perception, consciousness and memory. Thus, mutations in genes
involved in the specification and migration of neurons as well as the formation of the correct synapses
within the six-layered neocortex often lead to neurological diseases.
Recent discoveries of both gain- and loss-of-function mutations in the transcription factor FoxG1 inpatients with neurocognitive disorders strongly suggest that proper FoxG1 gene dosage is essential for
mental health. By taking advantage of mouse genetic strategies, I have revealed that FoxG1
expression levels change dramatically during the course of embryonic brain development in a mannerthat is tightly correlated with the differentiation and maturation stage of neurons. I have demonstrated
that these dynamic changes in FoxG1 expression are critical in the determination of the laminar
identity of pyramidal neurons. Furthermore, I have found that FoxG1 is required at distinct
developmental stages of GABAergic interneurons that play key inhibitory roles in the neocorticalcircuit.
These findings provide clarity as to the dose-dependent requirement for FoxG1 and why evenrelatively minor changes in its expression during development result in severe neurologicalimpairment.

References:
Miyoshi, G., and Fishell, G. (2012). Dynamic FoxG1 Expression Coordinates the Integration ofMultipolar Pyramidal Neuron Precursors into the Cortical Plate. Neuron 74, 1045-1058.

21

Yusuke Hirabayashi
Department of Neuroscience, Columbia University【Biographical Sketch】

2013 – present

Post Doctoral Fellow, Franck Polleux lab, Department of Neuroscience,
Columbia University

2013 – 2013

Research Associate, Franck Polleux lab, Department of Cell Biology, The
Scripps Research Institute2007 – 2013

Research Associate, Laboratory of Cell Signaling (Yukiko Gotoh Lab.),Institute of Molecular andCellular Biosciences, The University of Tokyo

2006 - 2007

Research Fellow, Laboratory of Cell Signaling (Yukiko Gotoh Lab.),Institute of Molecular and Cellular Biosciences, The University of Tokyo

22

Exploring the role of the mitochondria/endoplasmic reticulum (ER)interface in axonal development
Yusuke Hirabayashi and Franck Polleux
Columbia University- Department of Neuroscience- Mortimer B. Zuckerman Mind Brain Behavior
Institute- Kavli Institute for Brain Science, New York, NY 10032

Axon arborization and assembly of presynaptic terminals are critical for the formation of functional
neural circuits. Our group studies the role of the serine/threonine kinase LKB1 (also called STK11 or
Par4) in axon morphogenesis (Barnes et al. Cell 2007) and we recently discovered that LKB1 and oneof its 14 downstream kinase, NUAK1, controls axon branching by promoting mitochondria
immobilization at nascent presynaptic sites (Courchet, Lewis et al. Cell 2013). Importantly, the
LKB1-NUAK1 pathway immobilized mitochondria specifically at nascent presynaptic sites. These
results suggest that presynaptic mitochondria capture plays an important role in axonal/presynaptic
development. However, what anchors mitochondria at specific presynaptic sites is currently unknown.
The physical coupling of mitochondria with ER represents one of the best- characterized organelleinterface at least in simple eukaryotic cells such as yeast. We are currently testing the potential role ofmitochondria/ER coupling in the control of axon and presynaptic development. In the current study,
we developed novel ways to visualize this organelle interface in developing neurons and we examinedthe dynamics of ER/mitochondria interaction in developing axons. Our results suggest that the
mitochondria-ER interface might play a role in mitochondria localization presynaptically and thereby
might play a role during axon morphogenesis.

This work is supported by NINDS grant 9R01NS089456-06 (FP) and a JSPS grant for researchabroad (YH).

23

Wieland B. Huttner
Max Planck Institute of Molecular Cell Biology and Genetics,
Dresden, Germany【Biographical Sketch】

1976 – 1977

Postdoc, MPI for Experimental Medicine, Göttingen, Germany

1977 – 1980

Postdoc with Paul Greengard (Nobel Laureate 2000), Department of Pharmacology,
YaleUniversity, New Haven, USA

1981 – 1985

Junior Group Leader, MPI for Psychiatry, Munich, Germany

1985 – 1990

Group Leader, EMBL Cell Biology Programme, Heidelberg, Germany

1987 – 1991

Dean of Graduate Studies, EMBL PhD Programme, Heidelberg, Germany

1991 – 2000

Professor of Neurobiology and Chair, Institute of Neurobiology,
University of Heidelberg, Germany

1991 – 1999

Speaker, SFB 317 Molecular Biology of Neural Mechanisms and Interactions
University of Heidelberg, Germany

1992 – 2000

Speaker, “Graduiertenkolleg“ Molecular and Cellular Neurobiology
University of Heidelberg, Germany

1998 - present Director, MPI of Molecular Cell Biology and Genetics, Dresden, Germany
2001 - present Speaker, International Max Planck Research School
IMPRS-CellDevoSys, Dresden, Germany
2002 – present Honorary Professor of Neurobiology, Technische Universität Dresden, Germany
2004 – 2010

Member of the German Council of Science and Humanities ("Wissenschaftsrat")

2009 – 2012

Chair of the Scientific Council of the Max Planck Society

24

Neural stem and progenitor cells and neocortex expansion in development
and evolution
Wieland B. Huttner
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany

Our group studies the molecular and cellular mechanisms of neurogenesis in the developing neocortex
in the context of mammalian brain evolution, specifically the various types of cortical stem andprogenitor cells (CSPCs), their modes of division, their lineages, and the neuron production resulting
therefrom. With regard to (i) the site of mitosis and (ii) the absence or presence of ventricular contact
at mitosis, three principal classes of CSPCs can be distinguished. First, CSPCs that reside in theventricular zone (VZ) and that contact the ventricle where they undergo mitosis, i.e. theneuroepithelial cells, apical radial glial cells and apical intermediate progenitor cells, collectively
referred to as apical progenitors (APs). Second, CSPCs that reside in the subventricular zone (SVZ)
where they typically undergo mitosis and that have delaminated from the ventricle, i.e. the basal (orouter) radial glial cells and basal intermediate progenitor cells, collectively referred to as basal
progenitors (BPs). Third, CSPCs that undergo mitosis in the basal VZ or in the SVZ and that retain
ventricular contact at mitosis, called subapical progenitors.
Our group has been studying the following issues related to these CSPCs in the developing mouse,ferret, marmoset, macaque and human neocortex: (1) the various lineages from APs to BPs; (2) themachinery underlying BP delamination; (3) symmetric versus asymmetric cell divisions; (4) the
microcephaly gene Aspm; (5) the AP marker prominin-1/CD133; (6) membrane particles released
into the ventricle; (7) extracellular matrix, integrins, and progenitor self-renewal; (8) cell cycle length;(9) transcriptomes of embryonic mouse and fetal human neocortical germinal layers and specificprogenitor subpopulations.
Recent insights into the cell biology of CSPCs, molecular pathways and factors, and their role inneocortex expansion in development and evolution will be presented.

25Erich D. Jarvis
Associate Professor, Department of Neurobiology
Investigator, Howard Hughes Medical Institute
Duke University Medical Center, Box 3209
Durham, NC 27710【Biographical Sketch】

1979-1983

Scholarships to Geoffrey Ballet and Alvin Ailey Dance Schools, NY

1979-1983

Dance Major, High School of the Performing Arts, NY

1983-1988

B.A., Double: Biology & Mathematics. Minor: Chemistry. Hunter College, NY

1988-1995

Ph.D., Molecular Neurobiology & Animal Behavior, The Rockefeller University, NY

1995-1998

Postdoc. Molecular Neurobiology & Animal Behavior, The Rockefeller University,NY

1984-1988

Undergraduate: Molecular biology of protein synthesis genes in bacteria with Dr.
Rivka Rudner Hunter College, NY

1988-1995

Graduate, Molecular behavioral mechanisms of song-associative learning insongbirds with Dr. Fernando Nottebohm. The Rockefeller University, NY

1995-1998

Postdoc, Molecular biology of learned vocal communication in songbirds with Dr.
Fernando Nottebohm. The Rockefeller University, NY

1998-2002

Assistant Professor, Adjunct: The Rockefeller University, NY

1998-2005

Assistant Professor, Department of Neurobiology, Duke University Medical Center(DUMC), NC

1999-2005

Assistant Professor, Fellow: Center for Cognitive Neuroscience, Duke University,NC

2000-2005

Assistant Professor, Center for Bioinformatics & Computational Biology, Duke
University

2000-2005

Assistant Professor, Allied Faculty: Psychological & Brain Sciences, Duke University,NC

2001-2005

Assistant Professor, Faculty: Development Biology Program, DUMC, NC

2005-present

Associate Professor, Tenure: Neurobiology & departments above, Duke University,NC

2008-present

Investigator, Howard Hughes Medical Institute (HHMI)
26

Brain evolution of complex behavioral traits: vocal learning and spoken
language
Erich D. Jarvis
Department of Neurobiology, Duke University, Durham North Carolina USA; Howard Hughes
Medical Insitutes, Chevy Chase, Maryland USA

Understanding the evolution and mechanisms of how brain pathways for complex behaviors evolve as
been mysterious. One such trait is vocal learning, which is critical for song in song learning birds andspoken language in humans. Vocal learners have forebrain to brainstem vocal control systems, hereas
vocal non-learners only have brainstem vocal systems. We found that the specialized song learning
systems of songlearning birds (songbirds, parrots, hummingbirds) are embedded within an ancientertebrate motor system that controls limb and body movements. The song learning and adjacent motor
systems share many features in common, including motor-driven gene expression networks, and an
anterior pathway necessary for motor learning and a posterior pathway necessary for production oflearned movements. In addition, the song and speech learning pathways show convergent expression
changes in axon guidance molecules and other genes in song-learning birds and humans. To explainthese findings, I propose a motor theory of vocal learning origin, where ancient brain systems used tocontrol movement and motor learning gave rise, by brain pathway duplication, to brain systems tolearn and produce song and spoken language. The duplicated motor system is connected to muscles ofthe vocal organ to control a specialized form of learned movement control - song and speech, which
has specialized changes in genes involved in neural connectivity and neural activity. The auditorymotor connectivity of the vocal learning system in turn influences the adjacent motor system to allow
vocal learners to synchronize their body movements to rhythms in sounds heard, to learn to dance. In
this manner, the evolution of brain pathways for vocal learning have evolved independently of acommon ancestor, but dependent on a pre-existing motor learning pathway scaffold that then diverged.

References:
Pfenning et al. Convergent transcriptional specializations in the brains of humans and song learning
birds. (2014) Science 346 (6215): 1333 & 1256846-1 to -13.
Petkov and Jarvis. Birds, primates, and spoken language origins: behavioral phenotypes andneurobiological substrates. (2012) Front Evol Neurosci. 4(12):1-24.
Jarvis. Unsolved Mysteries: Vocal learning and spoken language: PLoS Biology (in review).

27

Noboru Hiroi
Professor of Psychiatry and Neuroscience
Albert Einstein College of Medicine of Yeshiva University
Noboru.hiroi@einstein.yu.edu【Biographical Sketch】

1995-1998

Associate Research Scientist, Division of Molecular Psychiatry, Department of
Psychiatry, Yale University School of Medicine, New Haven, CT

1998-2005

Assistant Professor of Psychiatry, Assistant Professor of Neuroscience, Director ofLaboratory of Molecular Psychobiology, Department of Psychiatry and Behavioral
Sciences and Department of Neuroscience, Albert Einstein College of Medicine,Bronx, NY

2005-2011

Associate Professor of Psychiatry, Associate Professor of Neuroscience, Director ofLaboratory of Molecular Psychobiology, Department of Psychiatry and Behavioral
Sciences and Department of Neuroscience, Albert Einstein College of Medicine,Bronx, NY

2006-2009

Visiting Scientist, RIKEN-Brain Science Institute (BSI), Wako, Saitama, Japan.
Noboru Hiroi, Ph.D.

2011-present

Associate Professor. Department of Genetics, Albert Einstein College of Medicine,Bronx, NY

2011-present

Professor of Psychiatry, Professor of Neuroscience, Director of Laboratory of
Molecular Psychobiology, Department of Psychiatry and Behavioral Sciences andDepartment of Neuroscience, Albert Einstein College of Medicine, Bronx, NY

28

Ontogeny of Autism: altered developmental trajectories of dimensionalfeatures of autism in genetic mouse models of 22q11.2 copy number
variants
Noboru Hiroi, PhD
Department of Psychiatry and Behavioral Sciences, Dominick P. Purpura Department of
Neuroscience, Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA

The precise mechanisms of autism spectrum disorders (ASDs) remain elusive. However, recently
discovered genetic variants have provided an unprecedented entry point to delve into the genetic
mechanisms of this developmental neuropsychiatric disorder. Chromosomal deletions andduplications, termed copy number variants (CNVs), are robustly and reproducibly associated with
ASDs. While CNVs at human chromosome 22q11.2 are associated with high rates of ASDs, how
22q11.2-encoded genes contribute to this developmental neuropsychiatric disorder is still poorly
understood. Gene dose alterations of small segments and individual genes in mice have identified
several 22q11.2 genes that contribute to various dimensional aspects of developmental
neuropsychiatric disorders. Our studies have identified the T-box transcription factor 1 (Tbx1) andCatechol-O-methyltransferase (COMT) as potential causative genes for dimensional aspects of
ASDs. Tbx1 heterozygous pups emit individually invariable call sequences as early as postnatal day 8
and such call sequences are ineffective in eliciting maternal approach. Moreover, Tbx1 heterozygosity
impairs reciprocal social interaction and working memory and enhances a repetitive behavioral trait.
COMT over-expression selectively impairs the developmental maturation of working memory
capacity during adolescence in mice. Our in vivo and in vitro data show that Tbx1 heterozygosity and
COMT over-expression affects postnatal neurogenesis. Taken together, defective postnatal
neurogenesis is a potential neuronal mechanism through which various dimensional features of ASDs
developmentally emerge.

References:
N. Hiroi, et al. A 200-kb region of human chromosome 22q11.2 confers antipsychotic-responsive
behavioral abnormalities in mice. Proc Natl Acad Sci U S A. 102(52),19132-7, 2005.
T. Hiramoto, et al. Tbx1: identification of a 22q11.2 gene as a risk factor for autism spectrum disorderin a mouse model. Hum. Mol. Genet. 20, 4775-4785 2011.
N. Hiroi, et al. Copy number variation at 22q11.2: from rare variants to common mechanisms ofdevelopmental neuropsychiatric disorders. Mol. Psychiatry 18, 1153-1165 2013.

29

Noriko Osumi
Department of Developmental Neuroscience Chair,Center for Neuroscience Director,
United Centers for Advanced Research & Translational Medicine (ART)
Tohoku University School of Medicine
osumi@med.tohoku.ac.jp【Biographical Sketch】
1979-1985

School of Dentistry, Tokyo Medical & Dental University

1985-1989

Graduate School of Dentistry, Tokyo Medical & Dental University

1989-1996

Research Associate, Department of Craniofacial Morphogenesis & Anomalies,
Tokyo Medical & Dental University

1996-1998

Associate Professor, National Institute of Neuroscience, National Center of
Neurology & Psychiatry

1998-

Present position

2007-

Special Advisor for Gender Equality (Tohoku University)

2007-

Member of Science Council of Japan

2008-2011

Distinguished Professor (Tohoku University)

2010-2011

Visiting Professor, MCB, Harvard University

2011-

Director of Core Center for Neuroscience

2012-

TWAS Associate Member

2014-

Associate Member of Science Council of Japan2015-

Director of United Centers for Advanced Research & Translational Medicine

30

Crosstalk between Pax6 haploinsufficiency and paternal aging inmodulating offspring behavior: a possible role for epigenetic modification
Noriko Osumi
Department of Developmental Neuroscience, Tohoku University Graduate School of Medicine,
Sendai, Japan

Human epidemiological studies have indicated that advanced paternal age is related in their offspring
to elevated rates of various psychiatric disorders such as schizophrenia, autism, early onset of bipolar
disorder, reduced IQ, and impaired social functioning in adolescence. Both genetic and epigenetic
mechanisms are assumed to be involved in these transgenerational effects. Currently, we are focusing
on elucidation of the epigenetic mechanism how paternal aging and paternal Pax6 haploinsufficiency
cause vocal communication deficits in F1 offspring, which was abolished when F2 offspring was born
to young F1 male mice. We have identified a common change of H3K79 tri-methylation (H3K79me3)
in both wild type (WT) and Pax6 mutant spermatocytes and sperm. Furthermore, a notable association
was observed between H3K79 tri-methylation of sperm versus age of male mice, and versus vocal
communication deficits in offspring. Based on these lines of evidence we favor to propose a scenariothat altered regulation of gene expression by H3K79me3 might be involved in a pathophysiologicalbasis of vocal communication deficits by advanced paternal aging. Identification of target genes
whose expressions are regulated by H3K79me3 will be warranted.

References:
Maekawa et al.: A novel missense mutation (Leu46Val) of PAX6 found in an autistic patient.
Neurosci Lett, 462(3), 267-271, 2009
Umeda et al.: Evaluation of Pax6 mutant rat as a model for autism. PLoS ONE, 5(12), e15500, 2010
Kimura et al.: Dynamic expression patterns of Pax6 during spermatogenesis in the mouse. J Anat (inpress)

31

Stephan J. Sanders
Department of Psychiatry, UCSF, San Francisco, USA
stephan.sanders@ucsf.edu【Biographical Sketch】

2003-2004

Pre-registration House Officer, Internal Medicine, General Surgery,
Paediatrics, Queens Medical Center, Nottingham, UK

2004-2005

Senior House Officer, Emergency Medicine, Derbyshire Royal Infirmary,
Derby, UK

2005-2006

Senior House Officer, Paediatrics and Neonatal Intensive Care, Northwick
Park Hospital, Harrow, London, UK

2006-2007

Senior House Officer, Paediatrics and Neonatal Intensive Care, Chelsea andWestminster Hospital, London, UK

2008-2011

Postdoctoral Research Associate, Child Study Center and Genetics, Yale
University Child Study Center, New Haven, CT

2011-2014

Graduate Student, Genetics, Yale University, New Haven, CT

2014-present

Assistant Professor, Psychiatry, University of California, San Francisco(UCSF), San Francisco, CA, USA

32

Genomic architecture and gene discovery in autism spectrum disorder
Stephan J Sanders, MD PhD
Department of Psychiatry, UCSF, San Francisco, USA

Autism spectrum disorder (ASD) is characterized by impairments in social communication andrestricted or repetitive behavior or interests. Heritability studies demonstrate a high genetic
contribution to ASD risk. Advances in genomic technology and statistical methods, along with theavailability of large cohorts of ASD families, have revolutionized our understanding of the genomicarchitecture of ASD and provided a mechanism for robust gene discovery. By integrating new andpreviously published data from ~2,500 families in the Simons Simplex Collection with published datafrom the Autism Sequencing Consortium and Autism Genome Project, we identify 71 unique risk loci
(6 multigenic loci and 65 genes) associated with ASD based on de novo and rare inherited variants.
Phenotypic analysis shows that the de novo mutations are observed more frequently in the presence offemale sex, low IQ, or seizures. The 65 risk genes form a cohesive network of protein-protein
interactions that is enriched for genes associated with chromatin regulation and synaptic function.

References:
Iossifov, I., O'Roak, B.J., Sanders, S.J., Ronemus, M., Krumm, N., Levy, D., Stessman, H.A.,
Witherspoon, K.T., Vives, L., Patterson, K.E., et al. (2014). The contribution of de novo coding
mutations to autism spectrum disorder. Nature 515, 216-221.
De Rubeis, S., He, X., Goldberg, A.P., Poultney, C.S., Samocha, K., Cicek, A.E., Kou, Y., Liu, L.,
Fromer, M., Walker, S., et al. (2014). Synaptic, transcriptional and chromatin genes disrupted in
autism. Nature 515, 209-215.
Pinto, D., Delaby, E., Merico, D., Barbosa, M., Merikangas, A., Klei, L., Thiruvahindrapuram, B., Xu,
X., Ziman, R., Wang, Z., et al. (2014). Convergence of genes and cellular pathways dysregulated in
autism spectrum disorders. Am J Hum Genet 94, 677-694.

33

Hidenori Yamasue
Department of Neuropsychiatry
Graduate School of Medicine
University of Tokyo
7-3-1, Hongo, Bunkyo-ku Tokyo 113-8655, Japan【Biographical Sketch】

2009-current

Associate Professor and Co-director, Department of
Neuropsychiatry,Graduate School of Medicine, University of Tokyo

2008

Associate Professor, Department of Neuropsychiatry, Graduate School of
Medicine, University of Tokyo

2006-2008

Assistant Professor, Department of Neuropsychiatry, Graduate School of
Medicine, University of Tokyo

2002-current

Visiting Researcher, Laboratory for Molecular Dynamics of Mental
Disorders, Brain Science Institute, RIKEN, Wako, Japan

2000- 2006

Specialty Doctor, Clinical and Research Fellow, Department of
Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo,
Japan

34

Crosstalk between neuroscience and clinical psychiatry with oxytocin in aneurodevelopmental disorder
Hidenori Yamasue
Department of Neuropsychiatry, School of Medicine, The University of Tokyo, Tokyo, Japan

Autism spectrum disorders, a highly prevalent neurodevelopmental disorder, currently have noestablished treatment for its core symptoms. The disorders are characterized by two core symptoms
including deficits in social communication and interaction, and repetitive and restricted behavior.
Since accumulating evidence supports the concept that oxytocin can induce effects on social andaffiliative behaviors, the neuropeptide is thought to be a potential therapeutic approach for deficits insocial communication and interaction in individuals with autism spectrum disorders. In fact, ourprevious studies have revealed oxytocin-induced temporal improvements of autistic behavior and its
neural basis such as brain activity. Ongoing studies are further conducting to examine several
unresolved issues such as 1) clinically meaningful effects after long-term administrations of oxytocin,2) bio-markers predicting individual differences in therapeutic effects in advance, and 3) potential
genetic and molecular mechanisms of effects of oxytocin on autism spectrum behaviors. In the forum,
integration of previous findings and introductions of ongoing studies will be presented to promote
productive interactions with other speakers and audiences from various research fields.

References:
Yamasue H et al.: Integrative approaches utilizing oxytocin to enhance prosocial behavior: fromanimal and human social behavior to autistic social dysfunction. J Neurosci 32(41), 14109-14117,
2012.
Watanabe T et al.: Mitigation of Sociocommunicational Deficits of Autism Through OxytocinInduced Recovery of Medial Prefrontal Activity: A Randomized Trial. JAMA psychiatry 71(2), 166175, 2014
Aoki Y et al.: Oxytocin improves behavioural and neural deficits in inferring others’ social emotionsin autism. Brain 137(Pt 11), 3073-3086, 2014
Aoki Y et al.: Oxytocin's neurochemical effects in the medial prefrontal cortex underlie recovery oftask-specific brain activity in autism: a randomized controlled trial. Mol Psychiatry 20(4), 447-453,
2015
Aoki Y, Yamasue H: Reply: Does imitation act as an oxytocin nebulizer in autism spectrum disorder?
Brain, First published online: 11 March 2015.

35

Yasuyuki Taki
Department of Nuclear Medicine and Radiology,
Institute of Development, Aging and Cancer,
Tohoku University
4-1 Seiryo-cho, Aoba-ku, 980-8575, Sendai Japanytaki@idac.tohoku.ac.jp【Biographical Sketch】

2003 – 2004

Medical Stuff, Tohoku University Hospital, Japan

2004 – 2008

Assistant Professor, Institute of Development, Aging and Cancer, Tohoku University,Japan

2008 – 2012

Associate Professor, Institute of Development, Aging and Cancer, Tohoku University,Japan

2012 - 2013

Professor, Tohoku Medical Megabank Organization, Tohoku University, Japan

2013 -present Professor, Institute of Development, Aging and Cancer, Tohoku University, Japan36

Brain development using magnetic resonance imaging in healthy children
Yasuyuki Taki
Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer,
Tohoku University, Sendai, Japan

Brain development continues throughout childhood and adolescence. It has been revealed that humanbrain development is structurally and functionally a non-linear process. In this review, we reviewed
the studies of brain development in healthy children, from the viewpoint of structure and perfusion ofgray matter and white matter. The trajectory of gray matter volume with age shows increase thendecrease, and the age at peak volume is different among brain regions in the first and second decadesof age. On the other hand, white matter volume increases mostly linearly during those periods. As forthe fractional anisotropy, most regions shows exponential trajectory with age during those periods. In
addition, the correlation between cerebral blood flow and age showed similar tendency of that of thegray matter volume. In addition, there are gender differences of brain structure and brain perfusion inregions such as the precuneus. Still, there are number of uninvestigated important issues, and futurestudies are expected to solve these issues.

References:
Taki Y, et al.: Linear and curvilinear correlations of brain white matter volume, fractional anisotropy,
and mean diffusivity with age using voxel-based and region-of-interest analyses in 246 healthy
children. Hum Brain Mapp, A34(8), 1842-56, 2013.
Taki Y, et al.: Linear and curvilinear correlations of brain gray matter volume and density with age
using voxel-based morphometry with the Akaike information criterion in 291 healthy children. Hum
Brain Mapp, 34(8), 1857-71, 2013.
Sassa Y, et al.: The correlation between brain gray matter volume and empathizing and systemizing
quotients in healthy children. NeuroImage, 60, 2035–2041, 2012.

37

Kenji J. Tsuchiya
Associate Professor
Hamamatsu University School of Medicine
Research Center for Child Mental Development andUnited Graduate School of Child Developmenttsuchiya@hama-med.ac.jp【Biographical Sketch】

2009 - Associate Professor (PI), Research Center for Child Mental Development,
Hamamatsu University School of Medicine
2009- Associate Professor (PI), Department of Epidemiology and Biostatistics, United Graduate
School of Child Development, Osaka University, Kanazawa University and Hamamatsu
University School of Medicine
2006-

Assistant Professor, Research Center for Child Mental Development, Hamamatsu University
School of Medicine

2003-

Assistant Professor, Department of Psychiatry and Neurology, Hamamatsu University Schoolof Medicine

2001-

Administrator and Staff Psychatrist, Tokyo Metropolitan Tama Centre for Mental Health2000-

Research Fellow, National Centre for Register-based Research, University of Aarhus

1999-

Researcher Fellow, Department of Psychiatric Demography, University of Aarhus

38

Neurodevelopmental Trajectories of Children with Autism Spectrum
DisorderKenji J. Tsuchiya
Hamamatsu University School of Medicine, Research Center for Child Mental Development,
Hamamatsu, Japan

Symptoms of autism spectrum disorder (ASD) can be detected as early as during the first two years oflife. The earliest symptoms of ASD include lack of a range of social skills and communicative skills,
although no single sign at any specific time point is sufficient to predict emergence of ASD.
Considering this lack of knowledge, researchers have addressed how neurodevelopmental trajectories
are different between children with and without ASD using (birth) cohort studies of high-risk children.
Birth cohorts of general population are also expected to address this lack of knowledge. Notably,
cohort studies of general population instead of selected population are highly beneficial because
contributions of risk factors to each neurodevelopmental trajectory can be estimated without biases. In
an attempt to do this, we founded a birth cohort study, Hamamatsu Birth Cohort for Mothers andChildren (HBC Study) with a sample of 1258 children born between 1 December, 2007 and 31
October, 2011 and their 1138 mothers. The participating children have been followed up for 7 times
during the first two years of life and 5 times during four more years (Tsuchiya et al., 2010; Takagai etal., under review). We have succeeded in extracting five classes of neurodevelopmental trajectories:
high normal, normal, low normal, delayed, markedly delayed. Further, each class has a different set ofrisk factors (Nishimura et al., under review). Finally, we have found that children who belong to low
normal, delayed, and markedly delayed class are solely associated with a risk for having ASD in along run. This suggests ASD can be subtyped according to early neurodevelopmental trajectory
patterns.

Reference:
Tsuchiya, K. J., Matsumoto, K., Suda, S., et al. (2010). Searching for very early precursors of autism
spectrum disorders: the Hamamatsu Birth Cohort for Mothers and Children (HBC). J Dev Origins
Health Disease, 1, 158-173.

39

Atsushi Senju
MRC Career Development Award Fellow
Reader in Social NeuroscienceCentre for Brain and Cognitive Development
Department of Psychological Sciences, Birkbeck College
The Henry Wellcome Building, Torrington Square, London WC1E 7HX

Research interests
My main research interest is the developmental origin of the "Social Brain" network, and its atypicaldevelopment in Autism Spectrum Disorder (ASD). Especially, I'm interested in how infants andchildren attend to, evaluate and react to others' social and communicative signal such as eye contact,
contingent movement and referential gaze/pointing. Currently I'm utilizing both behavioural andelectrophysiological measurement to tackle these questions.

【Biographical Sketch】

2002-2005

Research Fellow (DC1), Japan Society for the Promotion of Science, Tokyo, Japan(Supervisor: Toshikazu Hasegawa)2005, 2006

Researcher, Japan Agency of Science and Technology, Fukuoka, Japan

2005-2006

Leverhulme Trust Visiting Research Fellow, Birkbeck, University of London,
London, UK

2006-2008

ESRC/MRC Interdisciplinary Postdoctoral Fellow, Birkbeck, University of London,
London, UK

2008-2011

ESRC Research Fellow, Birkbeck, University of London, London, UK

2011-present

MRC Career Development Award Fellow, Birkbeck, University of London, London,UK

2014-present

Reader in Social Neuroscience, Department of Psychological Sciences, Birkbeck,
University of London, London, UK

40

Development of Spontaneous Social Cognition and Autism
Atsushi Senju
Centre for Brain and Cognitive Development, Birkbeck, University of London, London, UK

Most of human social interaction depends on spontaneous processing of social information embedded
in a natural and complex environment, and appropriate response in time. It contrasts with the majorityof standard assessment, in which the stimuli are well controlled and often isolated, the task and the
instruction is highly explicit and well instructed, and the participants often have enough time to think
and react. Here, I would like to present a series of researches exploring how humans process social
information spontaneously, which is demonstrated with eye-tracking methodology showing how
participants spontaneously shift their gaze adaptively when they observe social scene. I will also
summarize our research which explored how spontaneous social cognition develops, how thedevelopment could be affected by postnatal environment such as cultural and familial background,and how it is disturbed by developmental disorder such as autism.

References:Senju, A., Southgate, V., White, S., & Frith, U. (2009). Mindblind eyes: An absence of spontaneous
theory of mind in Asperger syndrome. Science, 325, 883-885.
Senju, A., Tucker, L., Pasco, G., Hudry, K., Elsabbagh, M., Charman, T., & Johnson, M. H. (2013).
The importance of the eyes: communication skills in infants of blind parents. Proceedings of theRoyal Society B: Biological Sciences, 280(1760).
Senju, A., Vernetti, A., Kikuchi, Y., Akechi, H., & Hasegawa, T. (2013). Cultural modulation of faceand gaze scanning in young children, PLOS ONE, 8, e74017.

41

Yoko Kamio
Department of Child and Adolescent Mental Health,National Institute of Mental Health,National Center of Neurology and Psychiatry, Tokyo, Japankamio@ncnp.go.jp

Academic field
Child psychiatry, particularly autism and related developmental disorders【Biographical Sketch】

1992-2001

Junior Lecturer, Department of Psychiatry, Kyoto University;

2000-2001

Visiting Research Fellow, Department of Psychology, University of Connecticut

2001-2006

Associate Professor, Department of Clinical Psychology, Kyushu University

2006–present

Director of Department of Child and Adolescent Mental Health, National Institute of
Mental Health, National Center of Neurology and Psychiatry, Japan42

Early detection and early intervention for ASD during life course
development: Not only for social-communication problems but also fordiverse mental health issues
Yoko Kamio
Department of Child and Adolescent Mental Health, National Institute of Mental Health, National
Center of Neurology and Psychiatry, Tokyo, Japan, kamio@ncnp.go.jp

Autism spectrum disorder (ASD) is a heterogeneous syndrome that includes both syndromic autism(to a lesser degree) and idiopathic autism (to a much greater degree), which has diverse manifestations
across the life course not only at a group level but also at an individual level. This diversity seems to
be common across ethnicities and cultures; that is, ASD may be culture free, although there are no
official representative data in Japan at present. Nonetheless, it is essential to consider the sociocultural context when developing evidenced-based early interventions for ASD and disseminatingthem to the entire child population with ASD and their families across Japan.
Given this, this presentation will address; 1) enhancement of early detection by complementing theexisting community developmental surveillance system with an ASD screening tool; 2) the unmet
clinical needs of community toddlers with high autistic symptoms including those relating to sleep,
irritability, fear and anxiety, and sensory problems; 3) how early symptoms found at around 2 years ofage can predict later psychopathology; 4) the long-term impact of early intervention for individuals
with normal IQ ASD. Finally, instead of targeting the entire ASD population, an endophenotype
approach is required for translational research. This presentation will also include our findings about
sensory hypersensitivity.

References:
Kamio et al.: Acta Psychiatrica Scandinavica, 128(1), 45-53, 2013
Kamio et al.: Autism, 17 (1): 16-27, 2013
Kamio et al.: J Aut Dev Disord, 44 (1), 194-203, 2014
Takahashi et al.: Molecular Autism, 5(1):23, 201443

Masahiro Hirai
Functional Brain Science Lab,
Center for Development of Advanced Medical Technology,
Jichi Medical University, Tochigi, Japan【Biographical Sketch】

2013 – present

Associate Professor, Jichi Medical University

2012

Visiting Researcher, JSPS Researcher Exchange Program(Central European University, Hungary)2011 – 2013

Researcher (Institute for Developmental Research, Aichi
Human Service Center, Japan)

2009 – 2011

JSPS Postdoctoral Fellowship for Research Abroad (Queen's
University, Canada)

2006 – 2009

Japan Society for the Promotion of Science (JSPS) Research
Fellowship for Young Scientists (National Institute forPhysiological Sciences, Japan)

2005 – 2006

Postdoctoral Fellow (University of Tokyo)

44

Embodied cognition from inside out in atypical development
Masahiro Hirai
Functional Brain Science Lab, Center for Development of Advanced Medical Technology, Jichi
Medical University, Tochigi, Japan

Understanding another’s behavior and how other people see the world is one of the vital abilities for
us to live in our dynamic and fluid social world. In this talk, two aspects of the body perception fromtwo different views in atypical development will be discussed. The first view for observing the bodyand bodily motion from the outside, our series of electrophysiological and behavioral studies on
action perception in people with autism spectrum disorders (ASD) and Williams syndrome (WS) will
be reported. The second view for observing the body from the inside, a series of studies on visualperspective taking (VPT) where the ability of understanding, taking into account what and how they
see will be presented. The results showed that the ability of VPT was impaired compared to that of themental rotation task in people with WS and this difficulty may be due to an inability to accurately
simulate mental body motion. These results indicate both aspects of body perception – inside andoutside - may be impacted in people with neurodevelopmental disorders. The relationship between theatypical body perception and social cognition will be discussed further.

References:
Hirai et al.: Body configuration modulates the usage of local cues to direction in biological motion
perception. Psychological Science, 22(12), 1543-1549, 2011
Hirai et al.: Developmental changes in mental rotation ability and visual perspective-taking inchildren and adults with Williams Syndrome, Frontiers in Human Neuroscience, 7, 856 (13 pages),2013
Hirai et al.: Differential electrophysiological responses to biological motion in children and adults
with and without autism spectrum disorders. Research in Autism Spectrum Disorders, 8(12) 16231634, 201445

Paul McMAHAN Matthews
Edmond and Lily Safra Chair, Head,
Division of Brain Science
Department of Medicine Imperial College London
and Centre for Neurotechnology【Biographical Sketch】
2014- present

Edmond and Lily Safra Professor of Translational Neuroscience and Therapeutics,
Division of Brain Sciences, Department of Medicine, Imperial College London

2012- present

Professor and Head, Division of Brain Sciences, Department of Medicine, Imperial
College London

2012- 2014

Vice-President for Integrative Medicines Development, Neurosciences and Medicine
Development Lead, GlaxoSmithKline (joint appointment with Imperial College)

2011-2012

Vice-President for Imaging; Head, Global Imaging Unit (GIU), Center for ClinicalStudies Excellence, GlaxoSmithKline.

2005-2011

Vice-President for Imaging; Head, GSK Clinical Imaging Centre (CIC),
GlaxoSmithKline.

2006-2008

Vice-President for Imaging, Neurology and Genetics

2006-2013

Professor of Clinical Neurosciences, Centre for Neuroscience, Department ofMedicine

Postgraduate Training

Research
1982-1983

Postdoctoral Fellow, Dept. of Biochemistry and Clinical Magnetic ResonanceLaboratory, Radcliffe Infirmary, University of Oxford

1983-1984

Postdoctoral Fellow, Dept. of Pharmacology, Stanford University

1989-1990

Clinical Research Fellow (Neurogenetics), Montreal Neurological Institute, McGill
University

1990-1993

MRC (Canada) Clinician-Scientist, Genetics Laboratory, Department of Biochemistry,
University of Oxford

46

Imaging in large populations: better defining later life brain disease risks
in terms of development, exposure and aging
Paul M. Matthews, OBE, MD, DPhil, FRCP, FMedSci
Edmond and Lily Safra Chair, Head, Division of Brain Sciences, Department of Medicine Imperial
College London and Centre for Neurotechnology

Imaging, family history, genetics, lifestyle and exposure data promise new opportunities forunderstanding disease risk as an integrated outcome of developmental factors and environment.
New capabilities applied at large scale are offering an unprecedented opportunity to address thischallenge.
One of the most recent of these studies is the most ambitious to date. It is being developed within
the UK Biobank (www.ukbiobank.ac.uk/), a large prospective cohort that was established by the UK
Medical Research Council and Wellcome Trust as a resource for the investigation of risk factors for
major diseases and morbidities of middle and older age. 500,000 men and women aged 40-69 years
were recruited nationwide between 2006 and 2010. The baseline assessment was extensive, withdetailed information gathered on prevalent disease, diet, lifestyle, socioeconomic factors, education,
medications/ supplements and specific measurements such as blood pressure, weight, height, bioimpedance, grip strength and ultrasound measures of heel bone density and cognitive testing.
Biomarker and genetic data also are avalaible. Longitudinal follow up to death will continue withlinkage to medical records.
The UK Biobank thus combines great size, breadth and depth for a prospective longitudinal cohort
study. As incident cases accrue, it allows a broad range of health outcomes- particularly including
those for late life brain diseases to be related to a uniquely broad range of risk factors through casecontrol studies “nested” within the overall cohort.
Last year, the UK Biobank Imaging Enhancement was initiated with funding from the UK Medical
Research Council and the Wellcome Trust. The objective of the Imaging Enhancement is to provide
a comprehensive imaging assessment that will include 3T MRI of the brain including advanced DTI
and resting state fMRI for connectivity analysis; 1.5T MRI of the heart and upper abdomen; carotid
doppler and DEXA of whole body, on a total of 100,000 participants across England. During thefirst year, processes have been optimised ethical issues explored and the feasibility of this complex,
high throughput imaging demonstrated.
For my group, this resource will enable investigations of brain disease based on genetic andobservations of longitudinal changes in probands, along with observations of forme fruste of diseaseacross clinically healthy individuals sharing risk factors. One area of focus will be further testing of
the hypothesis that healthy age-related brain degeneration mirrors development, with the areas of thebrain thought to develop later also degenerating earlier. To illustrate how such large imaging
datasets can be used, I will review a pilot study of 484 healthy subjects that revealed a transmodal
network, the lifespan pattern of age-related changes in which highlighted ways in aging is related tothe patterns of development of the brain. This work provided evidence that the network of brain
regions which develops relatively late during adolescence shows accelerated degeneration in old age
compared with the rest of the brain and is characterized by areas of heightened vulnerability tounhealthy developmental and aging processes. This link between development, processes of aging
and cognitive outcomes provides a broad framework for consideration of many diseases of the brain.
Availability of large imaging datasets from UK Biobank and similar initiatives in the near future
should enable powerful explorations of this to be undertaken.
47

Abstracts for
Short Talks and Posters

48

Dmrt genes differentially participate in Cajal-Retzius cell development of
the cerebral cortex
Takako Kikkawa1, Nobuyuki Sakayori2, Hayato Yuuki1, Yu Katsuyama3, Noriko Osumi1
1. Department of Developmental Neuroscience, United Center for Advanced Research andTranslational Medicine (ART), Tohoku University School of Medicine, Sendai, Japan
2. Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical
University, Fukushima, Japan
3. Department of Organ Anatomy, Tohoku University School of Medicine, Sendai, JapanFor the development of the central nervous system, a large variety of neuronal cell types are needed tobe generated at defined times and locations. Cajal-Retzius (CR) cells are the first neurons generated
during corticogenesis and are essential pioneer neurons that control neuronal migration in the cortex.
CR cells are derived from specific regions within the cortex, i.e., the pallial septum (PS), pallialsubpallial boundary (PSB), and cortical hem (CH). However, the molecular mechanism underlying
the generation of CR cell subtype in distinct CR cell origins is poorly understood. We have previously
shown that Dmrta1 (double-sex and mab-3 related transcription factor like family A1) is expressed inneural stem/progenitor cells in the neocortex and regulates proneural genes downstream of Pax6. In
this study, we found that Dmrta1 was expressed in the PS, PSB, and a part of the CH, whereas Dmrt3
was strongly expressed in the CH. To reveal functions of Dmrta1 and Dmrt3 in the production of CR
cells from distinct origins, we observed CR cells in Dmrta1 and Dmrt3 knockout (KO) mice. We
found that Dmrt3 ablation decreased the number of p73-positive CR cells derived from the CH
compared with wild type (WT) mice because Dmrt3 KO mice have abnormal the CH structure.
However, there were no differences between WT and Dmrta1 KO mice in the numbers of p73positive CR cells in the caudal cortex. These results suggest that Dmrt3 is involved in thedevelopment of the CH-derived CR subtype. To more explore the functions among Dmrt family
members in CR cell development, measurement of the PS- and PSB-derived CR subtypes using
Dmrta1 and Dmrt3 KO mice is now in progress.

49

Imaging RNA in Living Neural Circuits with Hybridization-sensitive
Fluorescent Probes
Dan Ohtan Wang
iCeMS, Kyoto University

If we can “see” newly synthesized RNA in a living brain, we will have a sense of real-time
interactions between environment and genome. If we can do this at single-cell levels, we will knowwhat neural circuits are integrating synaptic inputs to genome and are making long-lasting changes totheir connectivity with newly expressed genetic information. In my presentation, I will introduce two
newly developed RNA labeling technologies that may be potentially used to achieve such goals in
living animal brains.

50Gene-activation-associated long non-coding RNAs for species-dependent
epigenome formation
Takuya Imamura
Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu
University, Fukuoka 812-8582, Japan

Brain morphology and function differ depending on mammalian species. Recent transcriptome
analyses have shown that long non-coding RNAs (ncRNAs) play prevalent roles in transcriptional
regulation. In particular, we have reported that promoter-associated ncRNAs (pancRNAs) activate thepartner gene expression via local epigenetic changes. Here, we identify thousands of genes under the
pancRNA-mediated transcriptional regulation in five mammalian species in common. In the mouse,
1) pancRNA-partnered genes show tissue-specific expression pattern, 2) expression of pancRNAs
significantly enriched H3K4me3 and H3K27ac marks towards the partner gene expression, 3)
H3K4me1 marks the pancRNA-partnered genes regardless of their expression level, and 4) C- or Gskewed motifs were exclusively overrepresented between -200 and -1 bp relative to the transcription
start sites of pancRNA-partnered genes. More importantly, the comparative transcriptome analysis
among five different mammalian species using a total of 25 counterpart tissues showed that overall
pancRNA expression profile exhibited extremely high species-specificity compared to that of mRNA,suggesting that a significant number of pancRNAs contributed to the enhancement of a set of partner
genes' expression in a sequence-specific manner. We conclude that the gain and/or loss of geneactivation-associated pancRNA repertories, caused by formation or disorganization of the genomic
GC-skewed structure, finely shapes tissue-specific pattern of gene expression according to a given
species.

51

Individual differences of courtship ultrasonic vocalizations and its neuronalcorrelates in male mice
Kouta Kanno1.2, Takefumi Kikusui1
1. Companion Animal Research, School of Veterinary Medicine, Azabu University
2. Research Fellow of Japan Society for the Promotion of Science

Sexually dimorphic displays observed in various animals have been shaped in the process of evolution.
Recently, among the displays, courtship vocalizations in mice has been noted as models for vocal
communication and social behavior in the fields of biolinguistics and autism research as well as
instinctive behavior. Male mice emit ultrasounds when encountering females. The ultrasoundvocalizations (USVs) contain song-like structure and recent studies have focused on the detailanalysis of the characteristics of the songs, such as syllable compositions or temporal sequence ofsyllables, which are regarded as a biolinguistic model of syntax. However, the point is, biological or
behavioral significance and neural mechanisms of the USVs has been poorly understood.
Here we demonstrated correlation of amount of emission in the USVs with emotional behaviors andneuronal activity. First, we quantified differences in amount of USVs among individuals (C57BL6/j
males), when encountering females. We conducted a behavioral battery and it revealed that amount of
USVs was an expression of sexual motivation because the amount of the emission was negatively
correlated with mount latency; males that emitted more showed mounting on a female with a shorter
latency. Furthermore, comparing males before and after castration, USVs was significantly decreased
after castration and testosterone replacement restored the USVs.
Next, we screened responsible brain regions for the USVs emission using immunohistochemistry forneuronal activity maker c-Fos. As a result, the number of c-Fos immunoreactive (ir) cells in theventral tegmental area (VTA) was significantly higher in the males that exhibited USVs than that inexhibited no USVs. Additionally, characteristic distribution of c-Fos-ir cells was observed in theposterior part of preoptic area (POA). The POA-VTA pathway has been known as an important one
for sexual motivation. On the other hand, c-Fos immunoreactivity was not observed in the bed nucleus,
which is known as the one that is activated by sexual experience.
The present study suggests that courtship vocalization is expression of sexual motivation related tosex hormones and can be applied for the tool to distinguish neuronal representation of sexualmotivation from that of sexual experience. It possibly contributes investigation for information
processing in the brain and its relation to the behavior as the outcome of the processing.

52

Neuronal activity dependent translocation of Btbd3 to the cytoskeleton isessential for proper dendrite development
Asuka Matsui, Mami U, Aya C Yoshida, Satomi S Kikuchi, Tomomi Shimogori
Lab for Molecular Mechanisms of Thalamus Development

Proper dendrite formation controlled by neuronal activity is essential for efficient neuronal circuit
formation, contributing to proper and effective information processing. In our previous study, we
reported that BTBD3 (BTB/POZ domain containing 3) plays a critical role on spiny stellate neurons
in mouse barrel cortex to control dendrite orientation toward higher neuronal activity. However, detailmolecular mechanism remains unknown how dendrite morphology is controlled by neuronal activity
and BTBD3. First we analyzed subcellular distribution of BTBD3 in primary dissociated corticalneurons and revealed that BTBD3 translocation to cytoskeleton is triggered by neuronal activity.
BTBD3 was localized with neuronal intermediate filaments but not with actin and microtubule. Next
we introduced variety of BTBD3 deletion variants to identify critical domain of BTBD3 for neuronal
activity dependent cytoskeletal translocation. We found that BTB domain is indispensable for activity
dependent subcellular translocation. Moreover, BTB domain lacking mutant lost ability to remove
excess dendrite in mouse barrel cortex. These results suggest that translocation of BTBD3 to thecytoskeleton is required for morphological change of dendrites. We will further examine how
neuronal activity triggers BTBD3 translocation, and also visualize the localization of BTBD3 anddendrite pruning process simultaneously in living neurons. These results will reveal detail molecularpathway for activity dependent dendrite patterning.

53

Neuronal subtype specification in establishing the cerebral cortex
Carina Hanashima
Laboratory for Neocortical Development, RIKEN Center for Developmental Biology, Kobe, JapanThe functional integrity of the vertebrate brain systems relies on the precisely coordinated productionof diverse neuron populations during development. Specifically in the mammalian neocortex,
progenitors produce distinct neuronal subtypes in a stereotypical order and establish a characteristic
six-layer structure. Although homologous domains exist in sauropsids, neither avian nor reptilian
dorsal pallium exhibits identical laminar structure despite some of the common gene expressions.
Therefore, an interesting question remains how the developmental program is uniquely orchestrated in
mammals to control the number and subtypes of neurons to assemble an elaborate neocortical circuit.
Previous work from the laboratory has shown that Foxg1, a forkhead transcription factor expressed in
the telencephalon, plays a key role in neocortical specification. Using conditional Foxg1 mutant mice,
we demonstrated that the onset of Foxg1 is necessary and sufficient to establish early neocortical geneprogram and simultaneously switch neurogenesis from earliest Cajal-Retzius (CR) cells to projection
neurons of the neocortex. Genome-wide transcriptome and chromatin immunoprecipitation further
revealed that Foxg1 binds to mammalian-conserved non-coding sequences to regulate early geneprogram in the neocortex. Consistent with these data, comparative studies using chick, gecko andmarmoset embryos show that Foxg1 target genes are differentially regulated amongst the mammalianand non-mammalian vertebrates. We further identified mammalian-specific CR-expressing genes that
may be involved in instructing the neocortical cytoarchitecture. These results imply that theacquisition of novel regulatory system and molecular diversity of CR cells may be a critical step inestablishing a laminated neocortex in mammalian vertebrates.

54

Analysis of Autism Susceptibility Candidate 2 gene during development
M. Hoshino, K. Hori
National Center of Neurology and Psychiatry, Department of Biochemistry and Cellular Biology,
Tokyo, Japan.
hoshino@ncnp.go.jp

Previous studies have demonstrated that mutations in Autism susceptibility candidate 2 gene
(AUTS2) are associated with wide range of psychiatric disorders including autism spectrum disorders,schizophrenia, intellectual disability, ADHD, dyslexia and epilepsy, its functional roles have not been
well understood. In this study, we reveal that AUTS2 protein activates Rac1 to induce lamellipodia,
but downregulates Cdc42 to suppress filopodia in neuronal cells. Loss-of-function experiments showthat AUTS2 is involved in neuronal migration and neuritogenesis in the developing brain. Moreover,Auts2-deficient mice display behavioral abnormalities including anxiety-related emotion and memory
formation. Thus, our findings indicate that AUTS2 contributes to cortical development and is critical
for the acquisition of neurocognitive functions.

55

Progress report of the Tohoku Medical Megabank Project Birth andThree-Generation Cohort Study (The BirThree Cohort Study)
Hirohito Metoki, Mami Ishikuro, Taku Obara, Yuki Sato, Masahiro Kikuya,
Shinichi Kuriyama, Atsushi Hozawa, Noriko Osumi, Hideyasu Kiyomoto,
Junichi Sugawara, Yoichi Suzuki, Teiji Tominaga, Nobuo Fuse, Naoko Minegishi,
Ichiro Tsuji, Shigeo Kure, Nobuo Yaegashi, Masayuki Yamamoto
Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
hmetoki@med.tohoku.ac.jp

Background
Great East Japan Earthquake and subsequent Tsunami Disaster attacked devastatingly wide area ofnorth east coast of Japan on March 11th, 2011. In general, cause of diseases were combination ofgenetic factors and environment factors. There is no reports whether the big disaster was associatedwith individual diseases beyond genetic factors. Especially in children, detailed analysis is needed todivide genetic factors and environment factors.
The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study (the BirThree
Cohort Study) is a population-based prospective cohort study with genetic data and family
relationships. This cohort is planned as comprehensive cohort regarding disease in a subject of allages including child development.

Study design
The BirThree Cohort Study is a population-based prospective cohort study which consists of threegeneration. At first, this study includes pregnant women and their fetus as probands. Next, weparticipate the partner of the pregnant women and his/her parents (if present) as well as the children of
the pregnant women (if any). The BirThree Cohort Study will include 70,000 participants: 20,000
pairs of pregnant women and their fetus, 10,000 fathers, 15,000 grandparents, and 5,000 siblings offetus respectively.

Recruitment
By the end of July, 32,647 subjects participated: 12,670 pairs of pregnant women and their fetus,
3,708 fathers, 3,209 grandparents, and 4,466 siblings of fetus. Babies given birth by the end of July
were 8,223.

56

Decreased volume in the brain of Pax6 heterozygous mutant rats: A
morphometric MRI study
Kotaro Hiraoka1, Akira Sumiyoshi2, Hiroi Nonaka2, Ryuta Kawashima2, Noriko Osumi3
1. Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University,
Sendai, Japan, khiraoka@cyric.tohoku.ac.jp
2. Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku
University, Sendai, Japan
3. Department of Developmental Neuroscience, Tohoku University Graduate School of Medicine,
Sendai, Japan

Pax6 is a highly conserved transcription factor among vertebrates and plays important roles indevelopment of organs. In development of the central nervous system, Pax6 pleiotropically regulates
various developmental processes. It regulates patterning of the neural tube, proliferation anddifferentiation of neuroepithelial cells, migration of neurons, and formation of neural circuits. Humansubjects with PAX6 mutations show various brain malformations and psychiatric and cognitive
disorders. We have revealed that Pax6 heterozygous mutant (rSey2/+) rats exhibit abnormal social
interaction in adult stage [1]. However, brain malformations in adult mutants underlying the
behavioral disorders are unknown. In this study, we investigated abnormal morphology of the brain inrSey2/+ rats using small-animal magnetic resonance imaging (MRI). Sixty 10-week-old rats
underwent brain MRI (29 rSey2/+ rats and 31 wild-type rats). T2-weighted images were acquired
using a 7.0-T small-animal MRI. The software SPM8 was used for image preprocessing and statisticalimage analysis. Through the preprocessing of images, normalized maps of the Jacobian determinant
which is a parameter for the expansion and/or contraction of brain regions were obtained for each rat.
In the voxel-by-voxel analysis, rSey2/+ rats showed significant volume decrease in the various
regions in the brain including the isocortex, cingulum, corpus callosum, hippocampus, thalamus, andmidbrain compared to wild-type rats. In the ROI analysis, rSey2/+ rats showed 3.4% volume decreasein the whole gray matter and 3.6% volume decrease in the whole white matter compared to wild-type
rats. In conclusion, volume is decreased in various gray and white matter regions of the brain inrSey2/+ rats. The mechanism undelying the volume decrease and concern of the volume decrease to
manifestation of the abnormal behaviors in rSey2/+ rats are to be clarified in future studies.

57

Dynamic expression pattern of Pax6 in the testis
Ryuichi Kimura, Kaichi Yoshizaki, Kohei Koike, Hitoshi Inada, Noriko Osumi
Department of Developmental Neuroscience, United Center for Advanced Research and Translational
Medicine (ART), Tohoku University School of Medicine, Sendai, Japan

Pax6 transcriptional factor is expressed in various stem/progenitor cells and control balance between
their proliferation and differentiation, although neither expression nor function of Pax6 has beenaddressed yet in the adult testis where spermatogenesis continues throughout life. In the present study,
we examined the expression and function of Pax6 in male germ cell line. The expression of Pax6 was
confirmed in 67.0% (40/58 cells) of Plzf positive spermatogonia. The expression of Pax6 was also
observed in almost all p63 positive primary spermatocytes (99.1%, 335/338 cells).To examine theexpression dynamics of Pax6 with progression of meiosis, we classified seminiferous epithelium into
12 stages based on cellular organization of seminiferous tubular in the cross section. Pax6 expression
was observed in the nucleus of round spermatids at the seminiferous epithelial stages I-V andpachytene spermatocytes in all seminiferous stages. Pax6 was not observed in pre-leptotene, leptotene
and zygotene spermatocyte. We found that Pax6 formed single dot-like structure in mid pachytene
spermatocytes that were observed in stage V-VIII seminiferous tubules. This dot like structure wasrevealed as XY body, a nuclear sub-region in which X and Y chromosome are silenced andcompartmentalized during meiosis. Pax6 accumulation on XY body was restricted in mid pachytene
spermatocytes, and Pax6 was excluded from XY body in late pachytene spermatocytes that wereobserved in stage X seminiferous tubules. These results may suggest a novel role of Pax6 in
spermatogenesis other than a conventional transcriptional factor.

58

Paternal Pax6 haploinsufficiency precociously accelerated vocal
communication deficits by advanced paternal aging
Kaichi Yoshizaki, Ryuichi Kimura, Kohei Koike, Hitoshi Inada, Noriko Osumi
Department of Developmental Neuroscience, United Center for Advanced Research and Translational
Medicine (ART), Tohoku University School of Medicine, Sendai, Japan

Human epidemiological studies have indicated that advanced paternal age is associated with various
psychiatric disorders in their offspring through genetic and/or epigenetic mechanisms. How paternal
aging affects specific traits in offspring is becoming a fundamental issue in biology. Here we foundthat vocal communication by maternal separation was impaired in F1 offspring derived from oldfather than that in F1 offspring derived from young or middle-aged. In addition, paternal Pax6
haploinsufficiency precociously induced the vocal communication deficits by advanced paternal age
in offspring that inherited Pax6 mutation. Intriguingly, these transgenerational phenotypes
disappeared in F2 offspring when they were born to young F1 male mice. Regarding the neuronal
activity, we focused on the paraventricular thalamus (PVT), amygdala, and piriformcortex because
they are the brain regions related with anxiety and also express Pax6. We found that the number of cfos+ cells in the PVT and amygdala was significantly decreased in F1 offspring derived from oldfather. These results suggest that vocal communication defects due to advanced paternal age might becaused by the absence of anxiety-related neural activity through epigenetic mechanisms. To uncoverunderlying epigenetic mechanisms, we are analyzing DNA methylation and/or histone modification in
sperm and would like to examine gene expression profiles in the pup brain derived from young andold male mice.

59

Dendritic morphology of cortical pyramidal neurons is regulated by the
dopaminergic signal in early postnatal mice
Sato, T.1, 2, Saito, T.3 and Osumi, N.1
1) Dev Neurosci, Grad Sch of Med, Tohoku Univ, 2) FRIS, Tohoku Univ, 3) Dev Biol, Grad Sch ofMed, Chiba Univ

It has been suggested that dopamine plays an important role in various brain functions including
cognition, reward and executive function in humans. Abnormality of the dopaminergic signal has
been thought to cause mental disorder, such as attention deficit hyperactivity disorder (ADHD) andschizophrenia. While many reports have investigated roles of the dopaminergic signal in adolescentand adult stages, there are few reports that show a developmental role of the dopaminergic signal inearly postnatal stages. We are trying to elucidate the role of the dopaminergic signal in neural circuit
formation in early postnatal mice. It has been shown that there are two types of dopamine receptors.
One is the D1-like family of dopamine receptors that activates the trimeric GTP-binding protein Gs
and increases the intracellular level of cAMP. Another is the D2-like family of dopamine receptors
that activates Gi and decreases the intracellular level of cAMP. We misexpressed dopamine receptor
D1 (Drd1a) or D2 (Drd2) in pyramidal neurons of the mouse prefrontal cortex by the in vivo
electroporation-based tetracycline system (Sato et al., Journal of Neuroscience Methods, 2013). When
Drd1a was misexpressed, basal dendrites became shorter than those of control. In contrast,
misexpression of Drd2 caused longer and straighter basal dendrites than those of control. These
results suggest that the dopaminergic signal may regulate dendritic morphology of cortical pyramidal
neurons in early postnatal stages. The dopaminergic signal may play an important role not only inadolescent and adult stages but also in early postnatal stages. Now we are trying to analyze themorphology of basal dendrites of Drd1a- or Drd2-deficient pyramidal neurons.

60Tohoku Forum for Creativity Thematic Program 2015

Frontiers of Brain Science
July 2015 – September 2015
International Symposia
Tools and Technologies（July 21 – 27, 2015）

Development and Disease（August 24 – 26, 2015）

Memory and Mind

（September 28 – 30, 2015）

Speakers Include
David Amaral

Howard Eichenbaum

Francois Guillemot

Wieland Huttner

Jeff Lichtman

Georg Northoff

Shinsuke Shimojo

Susumu Tonegawa

UC DAVIS

Boston University

MRC

Harvard University

Max Planck

University of Ottawa

CalTechMIT / RIKEN

Organizers
General Organizers

Tools and Technologies

Development and Disease

Memory and Mind

The Tohoku Forum for Creativity is the first international visitor research institute in Japan.
Our aim is to identify important problems across all fields of research,and to develop innovative ideas and deeper theoretical foundations through intensive, focused discussions.

www.tfc.tohoku.ac.jp
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