Japanese

Tohoku University Graduate School of Medicine
Department of Developmental Neuroscience

RESEARCH

Brain development and neurogenesis underlying brain evolution and mental illness

Our brain is the center for nervous and mental functions from sensory perception and motor control to learning and memory. How such a brain is formed during embryonic and postnatal development? To elucidate molecular mechanisms for mammalian brain development is also the key to understand brain evolution and neurodevelopmental diseases such as autism. Our laboratory is focusing on this fundamental and fascinating question by using state-of-art technologies such as genome editing, next generation sequencing, and super-resolution imaging. We are working on mice and rats because they are easy to handle in the lab and suitable as disease models.

The ongoing projects are 1) elucidation of mRNA transportation machineries within the neural stem/progenitor cell during corticogenesis, 2) effects of epigenetic modification due to sperm aging on brain development and behavior traits in offspring, and 3) roles of functional fatty acids in proliferation and differentiation of neural stem cells and glial cells.

We are interested in cellular and subcellular mechanism of cortical neurogenesis. Since the neural stem/progenitor cells in the cortical primordium, called radial glial cells (RG cells), stretch their thin processes to apical (ventricular) and basal (pial) surface, various molecules localized in specific positions within the RG cell. The current projects include identification of a cellular machinery for transportation of basally-localized molecules such as Cyclin D2, a key regulator of cell cycle, via a currently unveiled RNA binding protein.

Impairment of neural development cause neurodevelopmental disorders such as autism spectrum disorder (ASD). Patients with ASD exhibit social impairment including verbal and non-verbal communication deficits, and repetitive behaviors/restricted interests. A survey by the Centers for Disease Control and Prevention revealed that 1 in 88 children has been identified with an ASD in 2008, which is 5.98-fold higher than that in 1992 (about 1 in 526). Among possible factors involved in increased prevalence with ASD, advanced parental age at delivery is considered to be one of the biological explanations. Our aim is to understand how advanced parental age contributes to pathophysiology for ASD thorough the epigenetic changes in their sperm and brains.

Lipids, especially fatty acids, are important nutrients because they compose cellular structures and produce biologically active substances. We focus on effects of lipid intake on rodent neural stem cells and neural development. We have recently reported how imbalance of n-6 and n-3 polyunsaturated fatty acids during pregnancy and early lactation impairs offspring's brain development and subsequently induces anxiety. Glial cells are also a major component of the central nervous system, as well as neurons. In the mammalian brain, glial cells have the number of several - dozens of times in comparison with neurons. We want to clarify the function of fatty acid binding proteins in astrocytes.

Our lab is participating in Neuro Global Graduate Program, and suitable for students and young researchers to be trained and raised in an international atmosphere with foreign students over the world.

Biosketch

Prof. Osumi has graduated Tokyo Medical and Dental University, been given PhD thesis from the same university, and now is a professor of Tohoku University School of Medicine since 1998. She has become Vice President of Tohoku University from 2018. Her research background is developmental neurobiology, and more recently, she has much interest in DOHaD theory, and eagers to understand regulatory mechanisms for transgenerational effects of paternal aging that affects offspring’s behavior. She is currently a representative of Grant-in-Aid for Scientific Research on Innovative Areas (16H06524) “Integrative Research toward Elucidation of Generation of Brain Systems for Individuality” and a leader for Neuro Global Graduate Program.

Recent papers:

Yoshizaki K, Koike T, Kimura R, Kikkawa T, Oki S, Koike K, Mochizuki K, Inada H, Kobayashi H, Matsui Y, Kono T, Osumi N: Paternal age affects offspring's behavior possibly via an epigenetic mechanism recruiting a transcriptional repressor REST. bioRxiv doi: https://doi.org/10.1101/550095

Kikkawa T, Casingal CR, Chun SH, Shinohara H, Hiraoka K, Osumi N: The role of Pax6 in brain development and its impact on pathogenesis of autism spectrum disorder. Brain Res 1705, 95-103, 2019

Sakayori N, Kikkawa T, Tokuda H, Kiryu E, Yoshizaki K, Kawashima H, Yamada T, Arai H, Kang JX, Katagiri H, Shibata H, Innis SM, Arita M, Osumi N: Maternal dietary imbalance between omega-6 and omega-3 polyunsaturated fatty acids impairs neocortical development via epoxy metabolites. Stem Cells 34(2), 470-482, 2016

For more detail, see the link:
https://www.ncbi.nlm.nih.gov/pubmed/?term=Osumi+N

Research@Tohoku University
Neuro Global Program Tohoku University
Brain and Individuality
Frontiers of Brain Science
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