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分子病態研究部門

１　研究活動の概要・目的

分子病態研究部門では、脳発達障害の予防・治療に関する研究を行っています。具体的には、神経機能障害の病態およびそれらを引き起こすメカニズムを分子レベルで明らかにし、関連分子測定などによる診断法の確立を目指しています。また、薬剤を用いた効率的な神経機能の改善や、神経変性の予防、進行防止などの治療法確立に貢献することを目指しています。

２　研究内容紹介

包括的解析バッテリーを駆使した発達障害原因遺伝子の病態機能解析
分子病態研究部門では、知的障害(ID)、自閉性疾患(ASD)および乳幼児てんかんの病態形成メカニズムを分子から個体レベルで包括的に解明する研究を行っている。研究手法として“発達障害の病因・病態分子解析バッテリー”を独自に構築し、原因遺伝子の異常が引き起こす病態を in vivoと in vitro で解析している。具体的には、マウス子宮内胎仔脳遺伝子導入法を用いて研究対象遺伝子の発現を抑制・促進し、大脳皮質発生期の神経細胞移動、軸索伸長、樹状突起網形成、細胞周期、海馬歯状回顆粒細胞の形態形成を ex vivo で観察すると共に、初代培養海馬神経細胞を用いたシナプス形態、生化学・分子細胞生物学的解析を行う。神経細胞の局在・形態異常が観察された場合には、共焦点レーザー蛍光顕微鏡観察下でのライブイメージングで詳細に解析し、さらに、ノックダウンマウスの行動解析や電気生理学的解析も遂行可能である。私共の強みは、分子からマウス個体まで、一連の実験を包括的に完結できる点にある。この解析バッテリーを主軸に臨床各施設との共同研究を効果的に運用し、ID、ASD および乳幼児てんかんの病態関連分子に関する具体的な研究成果を挙げることで臨床との連携を推進している。
神経シナプス形成の分子機構の解析
自閉症や知的障害の背景としてシナプス形態や機能の異常が想定されている。そこで、シナプス形成に関与する蛋白質を同定し、その機能・性状解析を行う。この結果、シナプス形成の分子機構の一端を分子レベルで明らかにし、シナプスの異常に基づく神経系の発達障害の新規診断・治療法の開発に貢献することを目指す。
大脳皮質アストロサイトの発生異常によりもたらされる発達障害の病態理解
ヒトの脳は約100億個の神経細胞から成ると言われるが、脳内にはさらにその約10倍もの数のグリア細胞が存在する。アストロサイトはグリア細胞の中でも最も豊富に存在する細胞種であり、脳発生／発達過程において神経回路形成に重要な役割を果たす。アストロサイトは神経細胞と同様に発生過程で脳の最深部で誕生し、大脳皮質内へと移動して配置する。我々は自ら開発した遺伝子導入技術とライブイメージング法を駆使し、その発生異常と発達障害との関連を解明する。
ヒト脳固有の発生機序と発達障害発症機構との関連解明
ヒトの脳は進化過程で著しく巨大化し、高度な精神活動を担うに至った。これまで哺乳類脳の発生機序に関する多くの知見が、マウスをモデル動物として集積されてきた。しかしヒトとマウスでは脳の構造や機能が大きく異なり、知的障害や発達障害の病態理解のため、ヒト固有の発生機構の解明が待たれている。我々は主にマウスを研究対象としながらも、ヒトやその他の霊長類胎児脳との対比により、ヒト脳の独特な発生機構を理解し、またその違いを生み出す分子機構を解明する。

３　メンバー紹介

部長　永田浩一（ながた　こういち） https://researchmap.jp/nagata/
室長　田畑秀典（たばた　ひでのり）https://researchmap.jp/read0080134
研究テーマ１：
大脳皮質アストロサイトの発生異常によりもたらされる発達障害の病態理解
研究テーマ２：脳固有の発生機序と発達障害発症機構との関連解明
室長　伊東秀記 （いとう　ひでのり） https://researchmap.jp/read0006830
研究テーマ：海馬歯状回の発達における神経発達障害関連分子の機能解明
研究員　野田万理子（のだ　まりこ） https://researchmap.jp/tamayura5/
研究テーマ１：新規発達障害関連分子のマウス大脳皮質形成における機能解明
研究テーマ２：疾患iPSまたは疾患iPS由来NPCのマウス胎仔脳への移植による脳形成過程への影響
研究員　濱田奈々子（はまだ　ななこ）　https://researchmap.jp/cortico-genesis/
研究テーマ：てんかん、精神発達障害原因遺伝子の病態形成メカニズムの解明
研究員　西條琢真（にしじょう　たくま）　https://researchmap.jp/tnishijo
研究テーマ：発達障害の原因となる転写制御遺伝子異常の分子病態メカニズムの解明
リサーチレジデント　菅原涼太（すがわら　りょうた）
研究テーマ：発達障害関連遺伝子の分子病態機構の解明
研究助手　石黒智己、岩本郁子、羽根信子、永野崇子、河村則子、小菅宏子

４　活動内容

トピックス

2022年12月
神経機能を制御するアストロサイトが脳内に広く分布する仕組みを解明し、Nature Communications誌に発表しました。
この論文は特に重要であるとして、Editors' Highlightsに選ばれました。精神神経疾患の新たな病態理解につながることが期待されます。 (2022.12.6.)
2022年5月
「知的障害責任分子RAC3による神経発達障害の病態メカニズム」について、第86回日本生化学会中部支部例会・シンポジウムで発表しました。
この発表で、日本生化学会中部支部奨励賞を受賞しました。 　　　　　　
2018年9月
乳幼児期に発症する難治性てんかん「ウエスト症候群」の原因になる遺伝子異常を特定し、発症メカニズムを解明しました。その成果はBrain誌に掲載されました(2018.9.26)

５　研究業績←クリックで表示

著書・総説

Tabata H: Crosstalk between blood vessels and glia during the central nervous system development. Life 12(11): 1761, 2022.

Ito, H., Nagata, K: Functions of CNKSR2 and its association with neurodevelopmental disorders. Cells 11, 303, 2022.

Scala M, Nishikawa M, Nagata K, Striano P: Pathophysiological Mechanisms in Neurodevelopmental Disorders Caused by Rac GTPases Dysregulation: What’s behind Neuro-RACopathies. Cells 10:3395, 2021.

Ito H, Morishita R, Nagata K: Functions of Rhotekin, an effector of Rho GTPase, and its bindingpartners in mammals.Int J Mol Sci 19: 2121, 2018.

Ito H, Morishita R, Nagata K: Autism spectrum disorder-associated genes and the development of dentate granule cells. Med Mol Morphol 50:123-9, 2017.

Ito H, Morishita R, Tabata H, Nagata K: Visualizing septin and cell dynamics in mammalian brain slices. Methods Cell Biol ”Septins” 136: 295-309, 2016.

Tabata H, Nagata K: Decoding the molecular mechanisms of neuronal migration using in utero electroporation. Med Mol Morph 49: 63-75, 2016.

浜田奈々子，稲熊裕，永田浩一：発達障害の背景としての大脳皮質構築異常．生化学87: 205-208,2015．

Ito H, Morishita R, Tabata H, Nagata K: Roles of Rho small GTPases in the tangentially migrating neurons. Histol Histopathol 29:871-879, 2014.

原著論文

Safavian D1, Kim M1, Xie H1, El-Zeiry M1, Palander O1, Dai L1, Collins R1, Froese C1, Shannon R1, Nagata K, Trimble W1 (1University of Toronto): Septin-mediated RhoA activation engages the exocyst complex to recruit the cilium transition zone. J Cell Biol 222(4):e201911062, 2023.

Nishikawa M, Scala M1, Umair M2, Ito H, Waqas A3, Striano P1, Zara F4, Costain G5, Capra V4, Nagata K (1University of Genoa, 2Ministry of National Guard Health Affairs, 3University of Education, 4IRCCS Giannina Gaslini Institute, 5The Hospital for Sick Children): Gain-of-function p.F28S variant in RAC3 disrupts neuronal differentiation, migration and axonogenesis during cortical development, leading to neurodevelopmental disorder. J Med Genet 60: 223–232, 2023.

Goto N1, Nishikawa M, Ito H, Noda M, Hamada N, Tabata H, Kinoshita M1, Nagata K-I (1Nagoya Univ): Expression Analyses of Rich2/Arhgap44, a Rho Family GTPase-Activating Protein, during Mouse Brain Development. Dev Neurosci 45: 19-26, 2023.

Hamada N, Noda M, Ito H, Iwamoto I, Nagata K-I: Expression Analyses of Cep152, a Responsible Gene Product for Autosomal Recessive Primary Microcephaly, during Mouse Brain Development. Dev Neurosci 44: 162-170, 2022.

Hamada N, Iwamoto I, Noda M, Nishikawa M, Nagata K-I: Expression Analyses of Polo-Like Kinase 4, a Gene Product Responsible for Autosomal Recessive Microcephaly and Seckel Syndrome, during Mouse Brain Development. Dev Neurosci 44: 643-650, 2022.

Scala M1, Nishikawa M, Ito H, Tabata H, Khan T2, Accogli A1, Davids L3, Ruiz A4, Chiurazzi P5, Cericola G6, Schulte B7, Monaghan G K8, Begtrup A8, Torella A9, Pinelli M9, Denommé-Pichon A-S10, Vitobello A10, Racine C11, Mancardi M M12, Kiss C13, Guerin A13, Wu W2, Vila G E4, Mak C B14, Martinez-Agosto A J14, Gorin B M14, Duz B15, Bayram Y16, Carvalho MB C17, Vengoechea E J3, Chitayat D18, Tan Y T19, Callewaert B20, Kruse B6, Bird M L21, Faivre L10, Zollino M5, Biskup S7, Undiagnosed Diseases Network, Telethon Undiagnosed Diseases Program, Striano P1, Nigro V9, Severino M12, Capra V12, Costain G2, Nagata K-I (1University of Genoa, 2The Hospital for Sick Children, 3Emory Healthcare, 4Universitat Autònoma de Barcelona, 5Università Cattolica Sacro Cuore, 6Helios-Klinikum Hildesheim, 7Praxis für Humangenetik, 8GeneDx, 9Telethon Institute of Genetics and Medicine, 10Université de Bourgogne Franche-Comté, 11CHU de Dijon Bourgogne, 12IRCCS Istituto Giannina Gaslini, 13Queen's University, 14UCLA, 15Haseki Training and Research Hospital, 16Children's Hospital of Philadelphia, 17Pacific Northwest Research Institute, 18University of Toronto, 19University of Melbourne, 20Ghent University Hospital, 21University of California San Diego): Variant-specific changes in RAC3 function disrupt corticogenesis in neurodevelopmental phenotypes. Brain 145: 3308-3327, 2022.

Tabata H, Sasaki M1, Agetsuma M2, Sano H1, Hirota Y1, Miyajima M1, Hayashi K1, Honda T1, Nishikawa M, Inaguma Y, Ito H, Takebayashi H3, Ema M4, Ikenaka K2, Nabekura J2, Nagata K, Nakajima K1 (1Keio Univ, 2NIPS, 3Niigata Univ, 4Shiga Univ): Erratic and blood vessel-guided migration of astrocyte progenitors in the cerebral cortex. Nat Commun 13: 6571, 2022.

Nagai M1, Iemura K1, Kikkawa T1, Naher S1, Hattori S2, Hagihara H2, Nagata K, Anzawa H1, Kugisaki R1, Wanibuchi H3, Abe T4, Inoue K4, Kinoshita K1, Miyakawa T2, Osumi N1, Tanaka K1(1Tohoku Univ, 2Fujita Health Univ, 3Osaka City Univ, 4RIKEN): Deficiency of CHAMP1, a gene related to intellectual disability, causes impaired neuronal development and a mild behavioral phenotype. Brain Commun fcac220, 2022.

Nishijo T, Suzuki E1, Momiyama T1 (1Jikei Univ Sch Med): Serotonin 5-HT1A and 5-HT1B receptor-mediated inhibition of glutamatergic transmission onto rat basal forebrain cholinergic neurones. J Physiol 600: 3149-3167, 2022.

Nishikawa M, Ito H, Noda M, Hamada N, Tabata H, Nagata K: Expression analyses of Rac3, a Rho family small GTPase, during mouse brain development. Dev Neurosci 44:49-58, 2022.

Nakano S, Nishikawa M, Kobayashi T, Harlin EW, Ito T, Sato K, Sugiyama T, Yamakawa H, Nagase T, Ueda H: The Rho guanine nucleotide exchange factor PLEKHG1 is activated by interaction with and phosphorylation by Src family kinase member FYN. J Biol Chem 298:101579, 2022.

Nishikawa M, Ito H, Tabata H, Ueda H, Nagata K: Impaired Function of PLEKHG2, a Rho-Guanine Nucleotide-Exchange Factor, Disrupts Corticogenesis in Neurodevelopmental Phenotypes. Cells 11:696, 2022.

Ito H, Morishita R, Noda M, Ishiguro T, Nishikawa M, Nagata KI: The synaptic scaffolding protein CNKSR2 interacts with CYTH2 to mediate hippocampal granule cell development. J Biol Chem 297, 101427, 2021.

Noda M, Ito H, Nagata K: Physiological significance of WDR45, a responsible gene for β-propeller protein associated neurodegeneration (BPAN), in brain development. Sci Rep 11:22568, 2021.

Heishima K, Sugito N, Soga T, Nishikawa M, Ito Y, Honda R, Kuranaga Y, Sakai H, Ito R, Nakagawa T, Ueda H, and Akao Y: Petasin potently inhibits mitochondrial complex I–based metabolism that supports tumor growth and metastasis. J Clin Invest 131: e139933, 2021.

Nishikawa M, Ito H, Noda M, Hamada N, Tabata H, Nagata K: Expression analyses of PLEKHG2, a Rho family-specific guanine nucleotide exchange factor, during mouse brain development. Med Mol Morphol 54:146–155, 2021.

Hamada N, Iwamoto I, Nishikawa M, Nagata K: Expression analyses of mediator complex subunit 13-like: A responsible gene for neurodevelopmental disorders during mouse brain development. Dev Neurosci 43:43–52, 2021.

Hayase Y1, Amano S2, Hashizume K1, Tominaga T3, Miyamoto H4, Kanno Y1, Ueno-Inoue Y1, Inoue T1, Yamada M2, Ogata S1, Balan S5, Hayashi K1, Miura Y1, Tokudome K6, Ohno Y6, Nishijo T, Momiyama T7, Yanagawa Y8, Takizawa A2, Mashimo T2,4, Serikawa T2, Sekine A9, Nakagawa E1, Takeshita E1, Yoshikawa T5, Waga C1, Inoue K1, Goto Y1, Nabeshima Y10, Ihara N1, Yamakawa K11, Taya S1, Hoshino M1 (1National Cent Neurol Psychiatry, 2Kyoto Univ, 3Tokushima Bunri Univ,4Univ Tokyo, 5RIKEN Cent Brain Sci, 6Osaka Univ, 7Jikei Univ, 8Gunma Univ, 9Chiba Univ, 10Foundation Biomedical Res Innovation, 11Nagoya City Univ): Down syndrome cell adhesion molecule like-1 (DSCAML1) links the GABA system and seizure susceptibility. Acta Neuropathol Commun 8: 206, 2020.

Suliman-Lavie R1, Title B1, Cohen Y1, Hamada N, Tal M1, Tal N1, Monderer-Rothkoff G1, Gudmundsdottir B2, Gudmundsson K3,4, Keller J3,4, Huang G-J5, Nagata K, Yarom Y1, Shifman S1 (1Hebrew Univ of Jerusalem, 2National Inst Hlth, 3National Cancer Inst Frederick, 4Leidos Biomed Res Inc, 5Chang Gung Univ): Pogz deficiency leads to transcription dysregulation and impaired cerebellar activity underlying autism-like behavior in mice. Nat Commun 11:5836, 2020.

Ito H, Morishita R, Noda M, Iwamoto I, Nagata KI: Biochemical and morphological characterization of SEPT1 in mouse brain. Med Mol Morphol 53: 221-228, 2020.

Fukabori R1, Iguchi Y1, Kato S1, Takahashi K1, Eifuku S1, Tsuji S1, Hazama A1, Uchigashima M2, Watanabe M2, Mizuma H3, Cui Y3, Onoe H4, Hikishima K5, Yasoshima Y6, Osanai M7, Inagaki R7, Fukunaga K7, Nishijo T, Momiyama T8, Benton R9, Kobayashi K1 (1Fukushima Med Univ Sch Med, 2Hokkaido Univ, 3RIKEN Cent Biosystems Dynamics Res, 4Kyoto Univ, 5National Inst of Adv Indust Sci Tech, 6Osaka Univ, 7Tohoku Univ, 8Jikei Univ Sch Med, 9Univ of Lausanne): Enhanced retrieval of taste associative memory by chemogenetic activation of locus coeruleus norepinephrine neurons. J Neurosci 40: 8367-8385, 2020.

Hamada N, Ito H, Shibukawa Y1, Morishita R, Iwamoto I, Okamoto N1, Nagata KI (1Osaka Women’s and Children’s Hosp): Neuropathophysiological significance of the c.1449T>C/p.(Tyr64Cys) mutation in the CDC42 gene responsible for Takenouchi-Kosaki syndrome. Biochem Biophys Res Commun 529: 1033-1037, 2020.

Ibaraki K, Hamada N, Iwamoto I, Ito H, Kawamura N, Morishita R, Tabata H, Nagata K, Expression Analyses of POGZ, A Responsible Gene for Neurodevelopmental Disorders, during Mouse Brain Development. Dev Neurosci 41:139–148, 2019.

Komabayashi-Suzuki M1, Yamanishi E2, Watanabe C1,2,3, Okamura M1, Tabata H, Iwai R1,2, Ajioka I4, Matsushita J3, Kidoya H5, Takakura N5, Okamoto T6, Kinoshita K7, Ichihashi M6, Nagata K, Ema M3,8, Mizutani K1,2 (1Kobe Gakuin Univ, 2Doshisha Univ, 3Shiga Univ, 4Tokyo Med and Dent Univ, 5Osaka Univ, 6Kobe Gakuin Univ, 7Shiga Med Ctr Res Inst, 8Kyoto Univ): Spatiotemporally Dependent Vascularization Is Differently Utilized among Neural Progenitor Subtypes during Neocortical Development. Cell Rep 29: 1113-1129, 2019.

Ito H, Morishita R, Mizuno M, Tabata H, Nagata K: Rho family GTPases, Rac and Cdc42, control the localization of neonatal dentate granule cells during brain development. Hippocampus 29:569-578, 2019.

Noda M, Iwamoto I, Tabata H, Yamagata T1, Ito H, Nagata K (1Jichii Univ): Role of Per3, a circadian clock gene, in embryonic development of mouse cerebral cortex. Sci Rep 9: 5874, 2019.

Kato K1, Miya F2, Hamada N, Negishi Y1, Kishimoto N3, Ozawa H3, Ito H, Hori I1, Hattori A1, Okamoto N4, Kato M5, Tsunoda T2, Kanemura Y6, Kosaki K7, Takahashi Y8, Nagata K, Saitoh S1 (1Nagoya City Univ, 2Tokyo Medical and Dental Univ, 3Shimada Ryoiku Cntr, 4Osaka Women’s and Children’s Hosp, 5Showa Univ, 6Osaka National Hosp, 7Keio Univ, 8Nagoya Univ): MYCN de novo gain-of-function mutation in a patient with a novel megalencephaly syndrome. J Med Genet 0:1–8, 2018.

Ibaraki K, Mizuno M, Aoki H1, Niwa A1, Iwamoto I, Hara A1, Tabara H, Ito H, Nagata KI (1 Gifu Univ) : Biochemical and morphological characterization of a guanine nucleotide exchanger factor ARHGEF9 in mouse tissues. Acta Histochem Cytochem 51:119-128, 2018.

Ito H, Morishita R, Mizuno M, Kawamura N, Tabata H, Nagata K: Biochemical and morphological characterization of a neurodevelopmental disorder-related mono-ADP-ribosylhydrolase, MACRO domain containing 2. Dev Neurosci 40: 278-287, 2018.

Hamada N, Ogaya S1, Nakashima M2, Nishijo T3, Sugawara Y4, Iwamoto I, Ito H, Maki Y1, Shirai K5, Baba S6, Maruyama K1, Saitsu H2, Kato M7, Matsumoto M8, Momiyama T3, Nagata K (1Central Hosp, 2Hamamatsu Univ, 3Jikei Univ, 4Soka Municipal Hosp, 5Tsuchiura Kyodo Hosp, 6Seirei-Hamamatsu General Hosp, 7Showa Univ, 8Yokohama City Univ): De novo PHACTR1 mutations in West Syndrome and their pathophysiological effects. Brain 141:3098-3114, 2018.

Iwai R1, Tabata H, Inoue M1, Nomura K1, Okamoto T2, Ichihashi M2, Nagata K, Mizutani K2 (1Doshisha Univ, 2Kobe Gakuin Univ): A Prdm8 target gene Ebf3 regulates multipolar-to-bipolar transition in migrating neocortical cells. Biochem Biophys Res Comm495:388-394, 2018.

Ishizuka K1, Tabata H, Ito H, Kushima I1, Noda M, Yoshimi A1, Usami M2, Watanabe K3, Morikawa M1, Uno Y1, Okada T1, Mori D1, Aleksic B1, Ozaki N1, Nagata K-I (1Nagoya Univ, 2Kohnodai Hosp, 3Hiroshima City Cent Child Health Dev): Possible involvement of a cell adhesion molecule, Migfilin, in brain development and pathogenesis of autism spectrum disorders. J Neurosci Res 96 : 789-802, 2018.(K.I. and H.T. are co-first authors)

Ito H, Mizuno M, Noguchi K1, Morishita R, Iwamoto I, Hara A1, Nagata K (1Gifu Univ): Expression analyses of Phactr1 (phosphatase and actin regulator 1) during mouse brain development. Neurosci Res 128:50-57, 2018.

Oshikawa M1, Okada K1, Tabata H, Nagata K-I, Ajioka I1 (1Tokyo Med and Dental Univ): Dnmt1-dependent Chk1 pathway suppression is protective against neuron division. Development 144: 3303-3314, 2017.

Hamada N, Mizuno M, Tomita H, Iwamoto I, Hara A, Nagata K. Expression analyses of Dusp22 (Dual-specificity phosphatase 22) in mouse tissues. Med Mol Morphol418:475-481, 2017

Hamada N, Iwamoto I, Tabata H,Nagata K: MUNC18-1 gene abnormalities are involved in neurodevelopmental disorders through defective cortical architecture during brain development. Acta Neuropathol Comm 5: 92, 2017.

Honda A1, Ito Y1, Takahashi-Niki K1, Matsushita N2, Nozumi M1, Tabata H, Takeuchi K1,2, Igarashi M1 (1Niigata Univ, 2Aichi Med Univ): Extracellular Signals Induce Glycoprotein M6a Clustering of Lipid Rafts and Associated Signaling Molecules. J Neurosci 37: 4046-64, 2017.

Goto M1, Mizuno M, Matsumoto A1, Yang Z1, Jimbo EF1, Tabata H, Yamagata T1, Nagata K (1Jichi Med Univ): Role of a circadian-relevant gene NR1D1 in brain development: possible involvement in the pathophysiology of autism spectrum disorders. Sci Rep 7: 43945, 2017.

Inoue M1, Iwai R1, Tabata H, Konno D2, Komabayashi-Suzuki M1, Watanabe C1, Iwanari H3, Mochizuki Y3, Hamakubo T3, Matsuzaki F2, Nagata KI, Mizutani KI1 (1Doshisha Univ, 2RIKEN, 3Univ Tokyo): Prdm16 is crucial for progression of the multipolar phase during neural differentiation of the developing neocortex. Development 144: 385-399, 2017.

Matsunaga Y1, Noda M, Murakawa H2, Hayashi K1, Nagasaka A3, Inoue S1, Miyata T3, Miura T2, Kubo KI1, Nakajima K1 (1Keio Univ, 2Kyushu Univ, 3Nagoya Univ): Reelin transiently promotes N-cadherin-dependent neuronal adhesion during mouse cortical development. Proc Natl Acad Sci USA 114: 2048-2053, 2017.

Hamada N, Negishi Y1, Mizuno M, Miya F2, Hattori A1, Okamoto N3, Kato M4, TsunodaT2, Yamasaki M5, Kanemura Y6, Kosaki K7, Tabata H, Saitoh S1, Nagata K (1Nagoya City Univ, 2Tokyo Med Dent Univ, 3Osaka Med Ctr, 4Showa Univ, 5Takatsuki Gen Hosp, 6Osaka Natl Hosp, 7Keio Univ): Role of a heterotrimeric G-protein, Gi2, in the corticogenesis: Possible involvement in periventricular nodular heterotopia and intellectual disability. J Neurochem 140: 82-95, 2016.

Inaguma Y, Matsumoto A1, Noda M, Tabata H, Maeda A2, Goto M1, Usui D2, Jimbo EF1, Kikkawa K3, Ohtsuki M1, Momoi MY1, Osaka H1, Yamagata T1, Nagata K (1Jichi Med Univ, 2Hata Kenmin Hosp, 3Kochi Health Sci Ctr): Role of Class III phosphoinositide 3-kinase in the brain development: possible involvement in specific learning disorders. J Neurochem 139: 245-255, 2016.

YuanQ1, YangF2, XiaoY1, TanS1, HusainN1, RenM2, HuZ2, Martinowich K2, NgJS1, KimPJ1, HanW3, NagataK, WeinbergerDR2, JeHS1 (1Duke-Natl Univ of Singapore, 2Johns Hopkins Univ,3Singapore Bioimaging Consortium): Regulation of brain-derived neurotrophic factor exocytosis and gamma-aminobutyric acidergic interneuron synapse by the schizophrenia susceptibility gene dysbindin-1. Biol Psychiatry 80: 312-322, 2016.

Hamada N, Ito H, Nishijo T1, Iwamoto I, Morishita R, Tabata H, Momiyama T1, Nagata K (1Jikei Univ Sch Med): Essential role of the nuclear isoform of RBFOX1, a candidate gene for autism spectrum disorders, in the brain development. Sci Rep 6: 30805, 2016.

Ito H, Morishita R, Nagata K: Schizophrenia susceptibility gene product dysbindin-1 regulates the homeostasis of cyclin D1. Biochim Biophys Acta 1862: 1383-1391, 2016.

Yang Z1, Matsumoto A1, Nakayama K1, Jimbo FE1, Kojima K1, Nagata K, Iwamoto S1, Yamagata T1(1Jichi Med Univ): Circadian-relevant genes are highly polymorphic in autism spectrum disorder patients. Brain Dev 38: 91-9, 2016.

Inaguma Y, Ito H, Iwamoto I, Matsumoto A1, Yamagata T1, Tabata H, Nagata K (1Jichi Med Univ): Morphological characterization of Class III phosphoinositide 3-kinase during mouse brain development. Med Mol Morphol49: 28-33, 2016.

Giridharan VV1, Thandavarayan RA2, Arumugam S3, Mizuno M, Nawa H4, Suzuki K4, Ko KM5, Krishnamurthy P2, Watanabe K3, Konishi T3(1Nattraja College of Pharm, 2Houston Methodist Res Inst,3Niigata Univ of Pharm and Applied Life Sci, 4Niigata Univ,5Hong Kong Univ of Sci and Tech): Schisandrin B ameliorates ICV-infused amyloid β induced oxidative Stress and neuronal dysfunction through inhibiting RAGE/NF-κB/MAPK and up-regulating HSP/Beclin expression.PLoS One10:e0142483, 2015.

Hamada N, Ito H, Iwamoto I, Morishita R, Tabata H, Nagata K: Role of the cytoplasmic isoform of RBFOX1/A2BP1 in establishing the architecture of the developing cerebral cortex. Mol Autism 6:56, 2015.

Hashimoto H1, Yuasa S1, Tabata H, Tohyama S1, Seki T1, Egashira T1, Hayashiji N1, Hattori F1, Kusumoto D1, Kunitomi A1, Takei M1, Kashimura S1, Yozu G1, Shimojima M1, Motoda C1, Muraoka N1, Nakajima K1, Sakaue-Sawano A2, Miyawaki A2, Fukuda K1(1Keio Univ, 2RIKEN): Analysis of cardiomyocyte movement in the developing murine heart. Biochem Biophys Res Commun 464:1000-7, 2015.

Kanatani S1, Honda T1, Aramaki M1, Hayashi K1, Kubo K-I1, Ishida M1, Tanaka DH1, Kawauchi T1, Sekine K1, Kusuzawa S1, Kawasaki T2, Hirata T2, Tabata H, Uhlen P3, Nakajima K1(1Keio Univ, 2NIG, 3Karolinska Inst): The COUP-TFII/Neuropilin-2 is a molecular switch steering diencephalon-derived GABAergic neurons in the developing mouse brain. Proc Natl Acad Sci USA 112:E4985-94, 2015.

Lee S-A1, Kim S-M1, Suh BK1, Sun H-Y1, Park Y-U1, Hong J-H1, Park C1, Nguyen MD2, Nagata K, Yoo J-Y1, Park SK1 (1Pohang Univ, 2Univ Calgary): Disrupted-in-schizophrenia 1(DISC1) regulates dysbindin function by enhancing its stability. J Biol Chem 290:7087-96, 2015.

Tabata, H: Diverse subtypes of astrocytes and their development during corticogenesis. Front Neurosci 9: 114, 2015.

Mizuno M, Matsumoto A1, Hamada N, Ito H, Miyauchi A1, Jimbo EF1, Momoi MY1, Tabata H, Yamagata T1, Nagata K (1Jichi Med Univ): Role of an adaptor protein Lin-7B in brain development: possible involvement in autism spectrum disorders. J Neurochem 132:61-69 2015.

Inaguma Y, Ito H, Hara A1, Iwamoto I, Matsumoto A2, Yamagata T2, Tabata H, Nagata K (1Gifu Univ, 2Jichi Med Univ): Morphological characterization of mammalian Timeless in the mouse brain development. Neurosci Res 92: 21-28, 2015.

Kato T1, Abe Y1, Hirokawa S1, Iwakura Y1, Mizuno M1, Namba H1, Nawa H1 (1Niigata Univ) : Neurobehavioral differences between mice receiving distinct neuregulin variants as neonates; impact on sensitivity to MK-801.Curr Mol Med 15:222-36, 2015.

Mizutani Y1, Iwamoto I, Kanoh H1, Seishima M1, Nagata K (1Gifu Univ): Expression ofDrebrin, an actin binding protein, in basal cell carcinoma, trichoblastomaand trichoepithelioma. Histol Histopathol 29: 757-766, 2014.

Hashimoto H1, Yuasa S1, Tabata H, Tohyama S1, Hayashiji N1, Hattori F1, Muraoka N1, Egashira T1, Okata S1, Yae K1, Seki T1, Nishiyama T1, Nakajima K1, Sakaue-Sawano A1, Miyawaki A1, Fukuda K1 (1Keio Univ): Time-lapse imaging of cell cycle dynamics during development in living cardiomyocyte. J Mol Cell Cardiol 72: 241-249, 2014.

Nishimura YV1,2, Shikanai M1, Hoshino M3, Ohshima T4, Nabeshima Y5, Mizutani K2,Nagata K, Nakajima K1, Kawauchi T1,6 (1Keio Univ, 2Doshisha Univ, 3NCNP, 4Waseda Univ, 5FBRI, 6PRESTO) : Cdk5 and its substrates, Dcx and p27kip1,regulate cytoplasmic dilation formation and nuclear elongation in migratingneurons.Development 141: 3540-3550, 2014.

Joliot V1, Ait-Mohamed O1, Battistl V1, Pontis J1, Philipot O1, Robin P1, Ito H,Ait-Si-Ali S1 (1Paris Diderot Univ): The SWI/SNF subunit/tumor suppressor BAF47/INI1 is essential in cell cycle arrest upon skeletalmuscle terminal differentiation. PLoS One9:e108858, 2014.

Jiang M1, Wang Q1, Karasawa T, Koo JW1,2, Li H1, Steyger PS1 (1Oregon Health Sci Univ, 2Seoul Natl Univ): Sodium-glucose transporter-2 (SGLT2; SLC5A2) enhances cellular uptake of aminoglycosides. PLoS One 9:e108941, 2014.

Ito H, Morishita R, Iwamoto I, Nagata K: Establishment of an in vivo electroporation method into postnatal newborn neurons in the dentate gyrus. Hippocampus 24:1449-1457, 2014.

Karasawa T, Lombroso PJ1 (1Yale Univ): Disruption of striatal-enriched protein tyrosine phosphatase (STEP) function in neuropsychiatric disorders. Neurosci Res 89:1-9, 2014.