Tohoku University Graduate School of Medicine
Department of Developmental Neuroscience

Welcome, Mao, Lan-kun and Kaede!!!

Tin has spent five years in our lab, and moved to the US as a postdoc at Anton lab in North Carolina at the end of March. In return, Mao, Lan-kun and Kaede have joined our lab from April. Spring is always a season of encounters and partings.

Our digital/virtual/online activities have already become our normal daily life. We now appreciate its convenience not to go far away for a business trip, or even in a meeting at a different building in the same campus. Or, we do not need print many documents and instead just look at files on the monitor.

President of our Tohoku University, Dr. Hideo Ohno, talked to the students at the time of graduation in March that social distancing does not mean social isolation. We are connected.

Yeah, it’s true, but yet I think we are missing something like chance ideas…

Welcome, Sara, Jasper and John!!!

In this fall semester, our Tohoku University is gradually accepting international students to join our campuses. We are snow suffering the third pandemic wave of the COVID-19, but learning how to deal with the troubling virus; the ratio of severe patients are decreasing compared with the first wave.

Japan has fallen 30 years behind when it comes to digitalization. In my opinion, we can now perform digital transformation (DX) due to the COVID-19 because we need to accelerate promoting digitalization and push online. This can also promote innovations in the way of working, such as telework, which I believe will increase productivity.

This spring we welcome a new master course student, Mr. Shyu Manabe, from Hokkaido University, and a new researcher, Mr. Shohei Ochi, from Kyoto University. I am really sorry that we could not have a usual welcome party enjoying foods and drinks together.

Now under the BCP level 4, the lab activity is so much restricted, although we are not at the stage of lock-down as in many laboratories in the world.

Nine years ago when we suffered from the Great Earthquake in Northeast Japan, I came up with an intriguing idea of paternalaging and neurodevelopmental diseases. This year, I would like to encourage you to save your time to think of something interesting.

The year of 2020 has started. Our President Hideo Ohno gave us a New-Year greetings on January 6th when we officially start our work. 

In essence, he asked us to change our Tohoku University into better one, by quitting old-fashioned processes and integrating new and reasonable ones. His sense of impatience is based the situation of our society that is moving faster and faster basically due to advanced technologies of internet and computation. 

We need to adopt to move faster than before. However, we also appreciate time to time to have a relaxed time to think about new ideas and to chat with others face to face, which I believe important to create a better science.

I have also been working as Director of University Libraries since last year. Recently, the library has different functions such as serving an environment for students/researchers/citizens to actively learn by themselves. Among such functions, how to deal with electric journals is one of the big issues.

The university libraries pay “subscription fees” to publishers who provide various journals in packages. We researchers pay “APC” (Article Processing Charge) when we publish papers; the publishers get money from two sides.

I, as a PI, have decided to post our manuscripts first on bioRxiv, a preprint server governed by Cold Spring Harbor Press, and then submit to journals. Below are the two such examples.

Tatehana M et al.: Detailed profiles of histone modification in male germ line cells of the young and aged mice. bioRxiv 2019.
https://www.biorxiv.org/content/10.1101/635961v2. doi: https://doi.org/10.1101/635961

Yoshizaki K, et al.: Paternal age affects offspring's behavior possibly via an epigenetic mechanism recruiting a transcriptional repressor REST. bioRxiv. 2019
https://www.biorxiv.org/content/10.1101/550095v1 doi: https://doi.org/10.1101/550095

Good morning!
I am delighted to give a short speech in the beginning of today’s meeting.This is the 4th Annual Meeting of Developmental Neurobiology, a kind of alumni meeting for our laboratory, but this year we invited special guests outside of Japan, Prof. Francois Guillemot from Crick Institute, Dr. Nannan Guo from Harvard University, as well as Dr. Katsuyasu Sakurai from Tsukuba University.Nannan and Katsu are our ex-members.

Wakamatsu-san and me joined this Tohoku University in November of 1998, and we have established our lab in April of 1999, just 20 years ago.
The very first students were Masanori Takahashi in Jichii Medical University, who is here, and Yukinori Endo, who is now in FDA in the US.And then, our lab has grown and expanded.

Of course, there were various ups and downs.Lab itself is a kind of a living creature.Looking back on these 20 years, I just would like to say, we were lucky because we survived the big earthquake happened 8 years ago, March 11th in 2011.After that, our lab has become more internationalized.
Well, Nannan was the first foreign postdoc in our lab.

So, we had started this annual spring meeting 3 years ago, not only to have a good occasion to be stimulated by recent activities talked from our ex-lab members, but also to enjoy cherry blossoms; fortunately this year is almost full bloom! (Although it snowed last night!!!)

So, please enjoy science in a relaxed atmosphere.Today, we will have a special get-together after the meeting.

Thank you.

Happy New Year!!! I wish you more happiness and success for 2019.

Last year I had a chance to listen to a talk by Mr. Haruaki Deguchi, President of Ritsumeikan Asia Pacific University (APU). He does not have an academic career; he is rather a business person who launched an internet insurance company for the first time in Japan. I have known him as an author of books about human history for 5,000 years.

APU is a new private university in Beppu, with half of the students from abroad. The lectures are half in Japanese and half in English. Promotion videos produced by the students went viral on internet.

President Deguchi said that it is important for innovation and creativity to think vertically, horizontally, and data-based. In other words, we need to respect history, survey situation in the world, and analyze data. I think this is also true for our life and career as scientists. We should know previous achievement with questions not yet been solved, search for state-of-art technology to challenge, and analyze data obtained. You can promote good research by having you face such consciousness.

In September, I chaired a special lecture by Dr. Hideaki Sena, a famous Japanese novelist who graduated Tohoku University. The title of his talk is “Brain, Novel, and Artificial Intelligence: What Kind of Novels Our Brain Can Enjoy?”.

Now AI can win games of Go and Shogi (a chess-like board game), and various robots are working in modern life. Dr. Sena told us that AI can write a short story with punch line, but we do feel such a story interesting; the AI-made story cannot win at the contest of short novels.

In his opinion, AI can mimic our human brain at the level of the cortex, but not of the striatum that is related with emotion and motivation.

We feel interesting or fun when we notice an unexpected story beyond imagination; AI may be better at logical processes than human beings, yet it does not have imagination or lacks creativity.

AI will definitely continue to evolve, which may bring about better and convenient life for us. Well, we do not know whether it can reach to the next level or not.

I recently read books written by a Japanese writer who had a stroke and has sub-sequently been suffering from higher brain dysfunction. He realized during his recovery that his disabled situation is similar to that of his wife, who is diagnosed as a neurodevelopmental disorder.

For example, his wife has shorter working memory so that she cannot remember many things at one time to execute complicated tasks. Paying money at a convenience store can be such a difficult task; remembering the total amount of money, finding proper coins in the purse, picking up those coins and giving them to the casher, who seems to be waiting in patience… What a pressure!

So, neurodevelopmental disorders, which are caused by congenital and/or postnatal factors, can be considered to have a common neural basis with higher brain dysfunction, which can also be brought about by aging.

The modern society is facing with declining birthrate and aging. We need to accept a more number of disabled people and live better life together.

A new school calendar has started. We welcome two master course students, Masa and Nodoka, in our lab. Congratulations, Masa and Nodoka!!!

From this April, Dr. Hideo Ohno is assigned as the President of Tohoku University. I will serve as Vice President in charge of Public Relationship, Promotion of Diversity, and University Libraries.

I like books and thus the position as the Director of University Library is a happy surprise for me. Due to the rise of electrical information, the role of libraries has been changing rapidly. So, I appreciate my duty in this interesting and challenging era.

Of course, doing good science together is the most priority. Let’s enjoy!

I wish you more happiness and success for 2018.

Last year, our Tohoku University has been authorized as a “Designated National University”, together with other two universities, i.e., The University of Tokyo and Kyoto University.

According to the material released from MEXT, the Designated National Universities need to be at the highest level in regard with research activity, social cooperation and internalization.

Fortunately, our university has been promoting internationalization during the term of the 21st President, Dr. Susumu Satomi.

From next April, Dr. Hideo Ohno, will be in place of the 22nd President of Tohoku University. He is an authority in spintronics and has been nominated as Nobel Laureate. I do hope our university will further promote cutting-edge research in various fields.

Sometime ago, I read a book entitled “Confidence Code”. It explains why men are more confident, in general, than women and how this influences on career path etc. I introduced the book at Gender Gap Event in WCPG2017 meeting in Orlando, suggesting that confidence is NOT coded, rather imprinted by environmental factors from the very early postnatal stage.

To persuade science, it is important to have “self-confidence”. This is different from “self-respect”, which is linked to an attitude to avoid being mentally damaged. Eventually, the latter makes students to hesitate asking questions in lectures and seminars. Since the confidence is not coded, it can be trained from time to time. Let’s start from asking questions in the lab!!!

This month, we had the 2nd meeting of our research grant group, KOSEI SOUHATSU, in Gotemba with more than 100 participants. It was successful with a lot of discussion on what is “Individuality”. Prof. Yoichi Nabeshima, an advisor of our grant group, made comments at the end of the meeting. “To do good research, first we need to set our mind free, second we need to be well prepared, and third we need to have a strong spirit to finish it”. I thought I need to keep in mind especially the third one.

I would like to introduce another impressive words from Dr. Motoko Yanagida, a professor of nephrology at Kyoto University when she gave a talk at a career path seminar on July 10th. She said “Your own achievement can be small but must be scientifically correct”. Yes, this is exactly right!!!

On April 12th, we had a closed seminar for our reunion, networking, and enjoying cherry blossoms in the Katahira Campus. The name of the venue is “Cerisier”, meaning cherry blossom in French, which I myself have given to. We Japanese LOVE cherry blossoms so much, probably because we like something very fugacious; we can only appreciate the full bloom for a week. To persuade good science, however, we need a continuous effort.

Looking back 2016, I feel how fast time flies and how dramatic things have been changed. Especially, we are happy to welcome new students from various countries. Starting a new big project on “Individuality” is exciting, yet struggling. I hope everyone’s happiness and our lab’s success in science in a new field.

In September, another secretary has joined our lab, and in October, so as new foreign students and Japanese undergraduates in Medical School. We welcome you all!!! On the other hand, Dr. Tatsuya Sato moved to Graduate School of Informative Science as Associate Professor. Congratulations on his promotion!!!

Tohoku University has a policy of globalization during the term of our President Dr. Susumu Satomi. In reality, however, there are various difficulties to follow this trend. I think it will be nice to improve the situation one by one when we cope with such "un-global" issues together with our four foreign students.

For example, many official documents are written only in Japanese. Announcement via Group Ware is the same. We need to translate them every time in each laboratory, which means a large amount of wasteful spending of human resources within our entire faculty. This is a bad tradition of old universities.

French chemist and microbiologist Louis Paster said "There is no boundary in science, but scientists have their own homelands." Globalization will make us conscious of our own Japanese culture and of what we need to highly esteem.

Our group grant “Integrative Research toward Elucidation of Generative Brain Systems for Individuality” has recently been accepted by MEXT. We will start this new project together with researchers in wide fields not only of neuroscience but also of psychology, engineering, and mathematics. We would like to understand how individual differences or diversity is generated during development and evolution. We will focus on both genetic and environmental/epigenetic mechanisms. ELSI involved in research for individuality is also discussed. The kick-off meeting will be held in December in Sendai area.

From this April, we welcome a new student, Cristine Rosales Casingal, who entered PhD course. She is originally from Philippines, and has scientific background in microbiology and molecular biology. She has also an experience in bioinformatics. I believe her knowledge and skills will add new approaches and information to our lab. Cristine’s project is on the role of FMRP in brain development. Thus, Dr. Takako Kikkawa is a direct supervisor, and Ryuji Nakamura serves as a student mentor. Since our lab should be more foreigner-friendly, Ryuichi Kimura will handle “Englishnization” in our lab. Communication using non-native languages is sometimes stressful, but the modern science is based on English, which can occasionally tell a story more logically than Japanese. So, this is another phase of our lab.

How our brain is formed? Our laboratory aims to understand 1) the regulatory mechanisms of brain development, 2) lipid biology in the brain and nervous system, and 3) transgenerational epigenetics underlying offspring's behavior.

We have identified multiple functions of a transcription factor Pax6 that regulates proliferation and differentiation of radial glia (i.e., neural stem/progenitor cells) via its specific downstream molecule including a fatty acid binding protein Fabp7 and a transcription factor Dmrta1, respectively. Recently, we have found that FMRP, an RNA-binding protein responsible for fragile X syndrome, may also be regulated under Pax6 and function to transport mRNA (e.g., of Cyclin D2) to the basal end of the radial glial processes.

We are also working on elucidation of lipid signals on neurogenesis and glial differentiation especially focusing on brain-rich fatty acids such as docosahexanoic acid (DHA) and arachidonic acid (ARA) and their binding partner fatty acid binding protein (Fabp).

We are further challenging to understand genetic and epigenetic mechanisms for etiology of neurodevelopmental diseases such as autism spectrum disorder (ASD). A hint has come from the possibility that Pax6 and paternal aging may be involved in the pathophysiology of ASD. We are establishing mouse models for ASD to understand how paternal aging affects offspring's behavior.

I have started my research life from a study of craniofacial development. The face includes sensory organs located near the mouth that exist at the most anterior part of the body. My previous professor once told me “Face predicts the brain”, which seemed to direct my research from craniofacial development to brain development. This is also because I have much interest in psychology. Therefore, it is quite natural for me to enter the neural development field after I found Pax6 mutation in Small eye rat (Matsuo et al., Nat Genet, 1993).

Research in our lab has further been expanded from brain development to postnatal neruogenesis because Pax6, a key regulator of brain development, is expressed in neural stem cells throughout life. We have also s tudied lipid signals in brain development, neurogenesis and behaviors because Pax6 regulates expression of fatty acid binding protein Fabp7. Simultaneously, we have found a unique “transgenerational epigenetic phenomena” during the study of autism, a neurodevelopment disease.

Now, “neuroepigenetics” is the key to understand complexity of brain development and aging, neurogenesis, and animal behavior. Genetic programs, determined at the level of DNA, is overwritten epigenetically by various environmental factors such as nutrition, stress, aging, etc. A new Keystone Symposia meeting on this exciting research field has started (http://www.keystonesymposia.org/15B5), and a journal named “Neuroepigenetics” has recently launched.

Four years have passed since 3.11 disaster in 2011. During this month, Sendai City has welcomed many people including those from abroad who were related with UN World Conference on Disaster Reduction. This is a good opportunity for Sendai to be more globalized and internationalized.

We need not to decay the experience of the disaster, but simultaneously, Tohoku University should lead regeneration as the central university in these Tohoku areas. What we need as members of Tohoku University is to contribute by performing good science.

In our lab, the projects already done before the 3.11 have almost been published. Now we are in the phase to harvest big projects afterwards such as “Impact of balanced n-6/n-3 fatty acids on brain development” and “Resilient phenotypes against hearing loss in fatty acid binding protein 7-KO mice”. “Transgenerational epigenetic changes due to paternal aging affect offspring’s behaviors” also needs to be deepened.

From now, we can collaborate with Tohoku Medical Megabank Project (ToMMo), in which a huge genome cohort and biobanking are ongoing. Whole sequence data of 1000 Japanese people have already released from ToMMo.

> Tohoku Medical Megabank Organization (ToMMo)

From Tohoku University Archives

Tohoku University has established in 1907 as the 3rd Imperial University, but the root of Medical School can be traced back to Miyagi Prefectural Medical School. From 1915 to 1941, a famous neuroanatomist, Prof. Genosuke Fuse, worked in Medical School. The picture (right) is a model of the nervous system Prof. Fuse made.

The 12th President of our university was Prof. Koichi Motokawa, who developed an electroencephalograph for the first time in Japan. Prof. Motokawa also established Institute for Brain Disease belonging to the Medical School, which was reformed when our Graduate School has expanded.

Based on such a history, Global COE project on neuroscience supported by MEXT was led by Osumi during 2008-2012 FY. This activity has led to establishment of Tohoku Brain Science Center in Tohoku University and Center for Neuroscience in Medical School. Moreover, young researchers and students have gathered as Tohoku Branch of Society for Young Neuroscientists, which holds an annual retreat as Winter School.

From this January, I have started to send you a newsletter of our lab including various news, important deadlines, and some tips that might be of your help. Our lab has been established in November, 1998 based on research in the developmental biology of the nervous systems. “Development (both embryonic and postnatal)” means various biological changes according to time transition. Several years ago, our lab has further expanded our study to include changes due to aging as well as its transgenerational effects.

Our lab is working both on pure basic research that is just really INTERESTING, and on research targeting future clinical application. In either way, important this to remember is not to follow others’ previous studies, nor just to widen the research horizontally, but to challenge against the critical issue in the field where no one has ever reached. Everyday bench work is sometimes boring or tiring, but you should never forget to aim the goal beyond the lab work!