Molecular machinery for neuronal migration and epilepsy

• Project/Area Number: 24650184
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: 独立行政法人国立精神・神経医療研究センター
• Principal Investigator: HOSHINO Mikio 独立行政法人国立精神・神経医療研究センター, 神経研究所 病態生化学研究部, 部長 (70301273)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 神経発生 / 神経細胞移動 / てんかん / 精神発達遅滞 / 神経科学 / 発生・分化 / 脳・神経 / 脳神経疾患

Research Abstract

Neuronal migration is one of pivotal steps during brain development, whose malfunction causes epilepsy and/or mental retardation. We found that an autism-related gene regulates actin dynamics and participates in neuronal migration. Targeted disruption of the gene in mice results in abnormal behavior resembling some human psychiatric disorders. By screening of kinase inhibitors that affect neuronal migration in slice cultures, we identified some candidate kinases involved in neuronal migration. Although we generated mice carrying focal cortical dysplasia-lie structures in the brain, we could not detect epileptic symptoms among them.

Research Products

• [Journal Article] Temporal identity transition from Purkinje cell progenitors to GABAergic interneuron progenitors in the cerebellum. (2014)
  • Author(s): Seto Y, Nakatani T, Masuyama N, Taya S, Kumai M, Minaki Y, Hamaguchi A, Inoue YU, Inoue T, Miyashita S, Fujiyama T, Yamada M, Chapman H, Campbell K, Magnuson MA, Wright CV, Kawaguchi Y, Ikenaka K, Takebayashi H, Ishiwata S, Ono Y, Hoshino M.
  • Journal Title: Nature Communications Volume: 5 Issue: 1 Pages: 3337-3337
  • DOI: 10.1038/ncomms4337
  • Peer Reviewed
• [Journal Article] Specification of spatial identities of cerebellar neuron progenitors by ptf1a and atoh1 for proper production of GABAergic and glutamatergic neurons (2014)
  • Author(s): Yamada M, Seto Y, Taya S, Owa T, Inoue YU, Inoue T, Kawaguchi Y, Nabeshima Y, Hoshino M
  • Journal Title: J Neurosci Volume: 34 Issue: 14 Pages: 4786-4800
  • DOI: 10.1523/jneurosci.2722-13.2014
  • Peer Reviewed
• [Journal Article] Characterization of Olig2 expression during cerebellar development. (2014)
  • Author(s): Seto Y, Ishiwata S, Hoshino M.
  • Journal Title: Gene Expression Patterns Volume: 15(1) Issue: 1 Pages: 1-7
  • DOI: 10.1016/j.gep.2014.02.001
  • Peer Reviewed
• [Journal Article] Genetic dissection of plexin signaling in vivo (2014)
  • Author(s): Worzfeld T, Swiercz JM, Senturk A, Genz B, Korostylev A, Deng S, Xia J, Hoshino M, Epstein JA, Chan AM, Vollmar B, Acker-Palmer A, Kuner R, Offermanns S
  • Journal Title: Proc Natl Acad Sci USA Volume: 111 Issue: 6 Pages: 2194-2199
  • DOI: 10.1073/pnas.1308418111
  • Peer Reviewed
• [Journal Article] Infant calming responses during maternal carrying in humans and mice (2013)
  • Author(s): Gianluca Esposito, Sachine Yoshida (equal contribution)
  • Journal Title: Current Biology Volume: 23 Issue: 9 Pages: 1-7
  • DOI: 10.1016/j.cub.2013.03.041
  • Peer Reviewed
• [Journal Article] Atoh1 directs hair cell differentiation and survival in the late embryonic mouse inner ear (2013)
  • Author(s): Chonko KT, Jahan I, Stone J, Wright MC, Fujiyama T, Hoshino M, Fritzsch B, Maricich SM
  • Journal Title: Dev Biol Volume: 381 Issue: 2 Pages: 401-410
  • DOI: 10.1016/j.ydbio.2013.06.022
  • Peer Reviewed
• [Journal Article] A Sharp Cadherin-6 gene expression boundary in the developing mouse cortical plate demarcates future functional areal border (2013)
  • Author(s): 寺川洋平, 他4名
  • Journal Title: Cerebral Cortex Volume: (in prese) Issue: 10 Pages: 2293-2308
  • DOI: 10.1093/cercor/bhs221
  • Peer Reviewed
• [Journal Article] Origin of the brush cell lineage in the mouse intestinal epithelium (2012)
  • Author(s): Matthew Bjerknes, Cyrus Khandanpour, Tarik Moroy, Tomoyuki Fujiyama, Mikio Hoshino, Tiemo J.Klisch, Qian Ding, Lin Gan, Jiafang Wang, Martin G.Martin, Hazel Cheng
  • Journal Title: Developmental Biology Volume: 362(2) Issue: 2 Pages: 194-218
  • DOI: 10.1016/j.ydbio.2011.12.009
  • Peer Reviewed
• [Journal Article] A sharp Cadherin-6 gene expression boundary in the developing mouse cortical plate demarcates the future functional areal border. (2012)
  • Author(s): Terakawa YW, Inoue YU, Asami J, Hoshino M, Inoue T
  • Journal Title: Cerebral Cortex Volume: in press
  • Peer Reviewed
• [Journal Article] GABAergic neuron specification in the spinal cord, the cerebellum, and the cochlear nucleus. (2012)
  • Author(s): Kei Hori
  • Journal Title: Neural Plast. Volume: 2012 (2012) Pages: 921732-921732
  • DOI: 10.1155/2012/921732
  • Peer Reviewed
• [Journal Article] Neuronal subtype specification in the cerebellum and dorsal hindbrain (2012)
  • Author(s): Hoshino M
  • Journal Title: Dev Growth Differ Volume: (in press) Issue: 3 Pages: 317-326
  • DOI: 10.1111/j.1440-169x.2012.01330.x
  • NAID: 10031136904
  • Peer Reviewed
• [Journal Article] In utero gene therapy rescues microcephaly caused by Pqbp1-hypofunction in neural stem progenitor cells
  • Author(s): Ito H, Shiwaku H, Yoshida C, Homma H, Luo H, Chen X, Musante L, Fischer U, Frints S, Romano C, Ikeuchi Y, Shimamura T, Imoto S, Miyano S, Kawauchi T, Hoshino M, Sudol M, Arumughan A, Wanker E, Rich T, Schwartz C, Matsuzaki F, Bonni A, Kalscheuer V, Okazawa H
  • Journal Title: Molecular Psychiatry Volume: (in press)
  • Peer Reviewed
• [Presentation] Cytoskeletal regulation by AUTS2 in Neuronal migration and neuritogenesis (2014)
  • Author(s): Hori K, Nagai T, Shan W, Sakamoto A, Taya S, Abe M, Yamazaki M, Nakao K, Nishioka T, Sakimura K, Yamada K, Kaibuchi K, Hoshino M
  • Organizer: International Symposium"New Frontier of Neuropathology 2014"
  • Place of Presentation: Tokyo, Japan
• [Presentation] Sox9 controls oligodendrocyte differentiation in the cerebellum (2014)
  • Author(s): 橋本了哉,増山典久,川口義弥,秋山治彦,小泉修一,星野幹雄
  • Organizer: 第7回神経発生討論会
  • Place of Presentation: 吹田
• [Presentation] Roles of Meis1 in the development of cerebellar granule cells (2014)
  • Author(s): 大輪智雄,田谷真一郎,西岡朋生,中村卓郎,五飯塚僚,貝淵弘三,星野幹雄
  • Organizer: 第7回神経発生討論会
  • Place of Presentation: 吹田
• [Presentation] Prox1 switches Granule cell precursors from proliferative to differentiative state in cerebellum (2014)
  • Author(s): 宮下聡,瀬戸祐介,川口義弥,宗田孝之,星野幹雄
  • Organizer: 第7回神経発生討論会
  • Place of Presentation: 吹田
• [Presentation] Cytoskeletal regulation by AUTS2 in Neuronal migration and neuritogenesis (2014)
  • Author(s): Hori K, Nagai T, Shan W, Sakamoto A, Taya S, Abe M, Yamazaki M, Nakao K, Nishioka T, Sakimura K, Yamada K, Kaibuchi K, Hoshino M
  • Organizer: International Symposium “New Frontier of Neuropathology 2014”
  • Place of Presentation: Suzuki Memorial Hall, Tokyo Medical and Dental University, Tokyo, Japan
• [Presentation] Roles of Atoh1 and Atoh1-interacting molecules in the cerebellum and the midbrain (2013)
  • Author(s): Taya S, Owa T, Nishioka T, Kaibuchi K, Hoshino M
  • Organizer: 第6回神経発生討論会
  • Place of Presentation: 和光
• [Presentation] 新規自閉症感受性遺伝子Auts2の分子機能の解明 (2013)
  • Author(s): 堀啓,田谷真一郎,西岡朋生,熊ノ郷晴子,安部学,山崎真弥,崎村健司,貝淵弘三,星野幹雄
  • Organizer: 第6回神経発生討論会
  • Place of Presentation: 和光
• [Presentation] A genetic analysis of hypothalamic development and function using Ptf1a-genetically modified mice (2013)
  • Author(s): Fujiyama T, Nagaoka M, Kumanogoh H, Hayase Y, Funato H, Tanaka T, Imura A, Yanagawa Y, Magnuson M, Obata K, Kawaguchi Y, Nabeshima Y, Hoshino M
  • Organizer: 第6回神経発生討論会
  • Place of Presentation: 和光
• [Presentation] Temporal identity transition of cerebellar GABAergic neuron progenitors (2013)
  • Author(s): Seto Y, Nakatani T, Masuyama N, Taya S, Kumai M, Minaki Y, Hamaguchi A, Inoue Y, Inoue T, Fujiyama T, Yamada M, Magnuson M, Kawaguchi Y, Ikenaka K, Takebayashi H, Ishiwata S, Ono Y, Hoshino M
  • Organizer: 第6回神経発生討論会
  • Place of Presentation: 和光
• [Presentation] Sox9 controls oligodendrocyte differentiation in the cerebellum and the midbrain (2013)
  • Author(s): 橋本了哉,増山典久,川口義弥,秋山治一裕,竹林浩秀,石渡信一,尾野雄一,彦,星野幹雄
  • Organizer: 第6回神経発生討論会
  • Place of Presentation: 和光
• [Presentation] A genetic analysis of hypothalamic development and function by using Ptf1a-genetically modified mice (2013)
  • Author(s): Fujiyama T, Nagaoka M, Kumanogoh H, Hayase Y, Funato H, Yanagisawa M, Tanaka T, Imura A, Yanagawa Y, Magnuson MA, Wright CV, Obata K, Kawaguchi Y, Nabeshima Y, Hoshino M
  • Organizer: Neuroscience 2013, Society for Neuroscience's 43rd annual meeting
  • Place of Presentation: San Diego, USA
• [Presentation] 分化発生期と成体期における小脳バーグマングリアの系譜解析 (2013)
  • Author(s): 増山典久,橋本了哉,川口義弥,秋山治彦,星野幹雄
  • Organizer: 第36回日本神経科学大会
  • Place of Presentation: 京都
• [Presentation] 小脳顆粒細胞前駆体の分化制御におけるProx1の役割 (2013)
  • Author(s): 宮下聡,瀬戸祐介,川口義弥,宗田孝之,星野幹雄
  • Organizer: 第36回日本神経科学大会
  • Place of Presentation: 京都
• [Presentation] Sox9 controls oligodendrocyte differentiation in the cerebellum (2013)
  • Author(s): 橋本了哉,増山典久,川口義弥,秋山治彦,小泉修一,星野幹雄
  • Organizer: 平成25年度包括型脳科学研究推進支援ネットワーク夏のワークショップ
  • Place of Presentation: 名古屋
• [Presentation] 小脳顆粒細胞におけるMeis1の果たす役割 (2013)
  • Author(s): 大輪智雄,田谷真一郎,西岡朋生,中村卓郎,五飯塚僚,貝淵弘三,星野幹雄
  • Organizer: 平成25年度包括型脳科学研究推進支援ネットワーク夏のワークショップ
  • Place of Presentation: 名古屋
• [Presentation] Prox1 regulates the last mitosis of granule cell precursors (2013)
  • Author(s): 宮下聡,瀬戸祐介,川口義弥,宗田孝之,星野幹雄
  • Organizer: 平成25年度包括型脳科学研究推進支援ネットワーク夏のワークショップ
  • Place of Presentation: 名古屋
• [Presentation] てんかん自然発症ラット突然変異体の解析 (2013)
  • Author(s): 田谷真一郎,早瀬ヨネ子,山田真弓,籾山俊彦,西條琢真,三浦義記,大野行弘,今奥琢士,伊原信夫,天野殖,星野幹雄
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] Regulation of spatial identities of cerebellar neuron progenitors by bHLH transcription factors (2013)
  • Author(s): 山田真弓,瀬戸裕介,田谷真一郎,大輪智雄,井上由紀子,井上高良,川口義弥,鍋島陽一,星野幹雄
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] Temporal identity transition of GABAergic neuron progenitors in the cerebellum (2013)
  • Author(s): 瀬戸裕介,中谷智哉,増山典久,田谷真一郎,熊井実,皆木康子,浜口晶子,井上由紀子,井上高良,藤山知之,山田真弓,Magnuson MA,川口義弥,池中一裕,竹林浩秀,石渡信一,尾野雄一,星野幹雄
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] Sox9 controls oligodendrocyte differentiation in the cerebellum (2013)
  • Author(s): 橋本了哉,増山典久,川口義弥,秋山治彦,小泉修一,星野幹雄
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] Roles of Meis1 in the development of cerebellar granule cells (2013)
  • Author(s): 大輪智雄,田谷真一郎,西岡朋生,中村卓郎,五飯塚僚,貝淵弘三,星野幹雄
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] 小脳顆粒細胞におけるProx1の機能解析 (2013)
  • Author(s): 宮下聡,瀬戸祐介,川口義弥,宗田孝之,星野幹雄
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] 小脳顆粒細胞前駆体の分化制御におけるProx1の役割 (2013)
  • Author(s): 宮下聡，瀬戸祐介，川口義弥，宗田孝之，星野幹雄
  • Organizer: 第36回日本神経科学大会
  • Place of Presentation: 国立京都国際会館
• [Presentation] てんかん自然発症ラット突然変異体の解析 (2013)
  • Author(s): 田谷真一郎，早瀬ヨネ子，山田真弓，籾山俊彦，西條琢真，三浦義記，大野行弘，今奥琢士，伊原信夫，天野殖，星野幹雄
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸国際会議場
• [Presentation] Sox9 controls oligodendrocyte differentiation in the cerebellum (2013)
  • Author(s): 橋本了哉，増山典久，川口義弥，秋山治彦，小泉修一，星野幹雄
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸国際会議場
• [Presentation] Neuron subtype specification in the cerebellum (2012)
  • Author(s): Hoshino M
  • Organizer: Joint symposium between Max Planck Institute and National Center of Neurology and Psychiatry
  • Place of Presentation: Munich, Germany
• [Presentation] Analysis of a rat model for human temporal lobe epilepsy (2012)
  • Author(s): Hoshino M
  • Organizer: International Synapse Research Workshop 2012
  • Place of Presentation: Okazaki, Japan
• [Presentation] Transcriptional regulation of the diversity of cerebellar GABAergic neurons (2012)
  • Author(s): Seto Y, Nakatani T, Masuyama N, Minaki Y, Kumai M, Hamaguchi A, Kawaguchi Y, Ikenaka K, Takebayashi H, Ishiwata S, Ono Y, Hoshino M.
  • Organizer: Neuroscience 2012, Society for Neuroscience's 42nd annual meeting
  • Place of Presentation: New Orleans, USA
• [Presentation] Ptf1a遺伝子改変マウスを用いた視床下部の発生および機能の解析 (2012)
  • Author(s): 藤山知之,星野幹雄
  • Organizer: 平成24年度包括型脳科学研究推進支援ネットワーク夏のワークショップ
  • Place of Presentation: 仙台
• [Presentation] Characterization of a novel Autism-related gene in the CNS development (2012)
  • Author(s): Hori K, Taya S, Nishioka T, Kumanogoh H, Kaibuchi K, Hoshino M
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋
• [Presentation] A genetic analysis of hypothalamic development and function using Ptf1a-cre & Ptf1a-flox mice (2012)
  • Author(s): 藤山知之,早瀬ヨネ子,長岡麻衣,熊ノ郷晴子,柳川右千夫,マグヌソンマーク,小幡邦彦,田中智宏,伊村明浩,船戸弘正,川口義弥,鍋島陽一,星野幹雄
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋
• [Presentation] Temporal identity transition of GABAergic neural precursors in embryonic cerebellum (2012)
  • Author(s): 瀬戸裕介,中谷智哉,増山典久,皆木康子,熊井実,濱口晶子,川口義弥,池中一裕,竹林浩秀,石渡信一,尾野雄一,星野幹雄
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] 小脳発達制御因子Atoh1の結合分子の網羅探索および機能解析 (2012)
  • Author(s): 大輪智雄,田谷真一郎,西岡朋生,貝淵弘三,星野幹雄
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋
• [Presentation] Characterization of the molecular function for a novel Autism-related gene in the CNS development (2012)
  • Author(s): Hori K, Taya S, Nishioka T, Kumanogoh H, Abe M, Yamazaki M, Sakimura K, Kaibuchi K, Hoshino M
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] A genetic analysis of hypothalamic development and function using Ptf1a-genetically modified mice (2012)
  • Author(s): Fujiyama T, Nagaoka M, Kumanogoh H, Hayase Y, Funato H, Tanaka T, Imura A, Yanagawa Y, Magnuson M, Obata K, Kawaguchi Y, Nabeshima Y, Hoshino M
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] Transcriptional regulation of the diversity of cerebellar GABAergic neurons． (2012)
  • Author(s): Seto et al.
  • Organizer: Society for Neuroscience
  • Place of Presentation: 米国ニューオーリンズ カンファレンスセンター
• [Presentation] Analysis of a rat model for human temporal lobe epilepsy (2012)
  • Author(s): Hoshino M.
  • Organizer: International Synapse Research Workshop
  • Place of Presentation: 愛知県岡崎市 自然科学研究機構
  • Invited
• [Presentation] Neuron subtype specification in the cerebellum (2012)
  • Author(s): Hoshino M.
  • Organizer: Joint symposium between Max Planck Institute and NCNP（
  • Place of Presentation: ドイツ、マックスプランク研究所 リングバーグ城
  • Invited
• [Book] Specification of cerebellar and precerebellar neurons. Handbook of the Cerebellum and Cerebellar Disorders (2012)
  • Author(s): Hoshino M, Seto Y, Yamada M
  • Publisher: Springer, Netherlands
• [Book] 培養皿上の成熟神経細胞への遺伝子導入.実験医学別冊目的別で選べる遺伝子導入プロトコール (2012)
  • Author(s): 田谷真一郎,星野幹雄
  • Publisher: 羊土社,東京
• [Book] Specification of cerebellar and precerebellar neurons. HANDBOOK OF THE CEREBELLUM AND CEREBELLAR DISORDERS (2012)
  • Author(s): Hoshino M, Seto Y, Yamada M
  • Total Pages: 13
  • Publisher: Springer
• [Remarks]
  • URL: http://www.ncnp.go.jp/nin/guide/r_diag/index.html
• [Remarks] NCNP病態生化学研究部
  • URL: http://www.ncnp.go.jp/nin/guide/r_diag/index.html
• [Remarks] 国立精神神経医療研究センター神経研究所病態生化学研究部
  • URL: http://www.ncnp.go.jp/nin/guide/r_diag/index.html