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Molecular machinery for neuronal subtype specification in the cerebellum.

Research Project

Project/Area Number 24300138
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionNational Center of Neurology and Psychiatry

Principal Investigator

Hoshino Mikio  国立研究開発法人国立精神・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 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2014: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Fiscal Year 2013: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2012: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Keywords神経科学 / 発生・文化 / 脳・神経 / 発生・分化 / 脳神経疾患 / 神経化学 / 小脳 / 発生 / 幹細胞 / 神経系 / 転写因子 / 運命決定 / 変異マウス
Outline of Final Research Achievements

In this study, we generated two novel knock-in mouse lines, which are designed to express Atoh1 and Ptf1a ectopically in the VZ and RL, respectively. In those mutant mice, we observed glutamatergic and GABAergic neurons ectopically produced from Atoh1-expressing VZ and Ptf1a-expressing RL, respectively, suggesting that spatial identities of cerebellar neuron progenitors are regulated by Atoh1 and Ptf1a.
Within the cerebellar VZ at early stages, we find two types of progenitors; Olig2-expressing Purkinje cell progenitors (PCPs) and Gsx1-expressing Pax2-positive interneuron progenitors (PIPs). As development proceeds, PCPs gradually become PIPs starting from ventral to dorsal. The temporal identity transition of cerebellar GABAergic neuron progenitors from PCPs to PIPs is negatively regulated by Olig2 and positively by Gsx1.
These findings contribute to understanding spatiotemporal control of neuronal progenitor identities by transcription factors.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (37 results)

All 2016 2015 2014 2013 2012 Other

All Journal Article (17 results) (of which Peer Reviewed: 17 results,  Acknowledgement Compliant: 3 results,  Open Access: 3 results) Presentation (17 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Origins of oligodendrocytes in the cerebellum, whose development is controlled by the transcription factor, Sox92016

    • Author(s)
      Hashimoto R, Hori K, Owa T, Miyashita S, Dewa K, Masuyama N, Sakai K, Hayase Y, Seto Y, Inoue YU, Inoue T, Ichinohe N, Kawaguchi Y, Akiyama H, Koizumi S, Hoshino M
    • Journal Title

      Mech Dev

      Volume: 140 Pages: 25-40

    • DOI

      10.1016/j.mod.2016.02.004

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Heterozygous Disruption of Autism susceptibility candidate 2 Causes Impaired Emotional Control and Cognitive Memory.2015

    • Author(s)
      Hori K, Nagai T, Shan W, Sakamoto A, Abe M, Yamazaki M, Sakimura K, Yamada K, Hoshino M.
    • Journal Title

      PLoS One

      Volume: 30 Issue: 12 Pages: e0145979-e0145979

    • DOI

      10.1371/journal.pone.0145979

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Classic cadherin expressions balance postnatal neuronal positioning and dendrite dynamics to elaborate the specific cytoarchitecture of the mouse cortical area2015

    • Author(s)
      Egusa SF, Inoue YU, Asami J, Terakawa YW, Hoshino M, Inoue T
    • Journal Title

      Neurosci Res

      Volume: 105 Pages: 49-64

    • DOI

      10.1016/j.neures.2015.09.006

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In utero gene therapy rescues microcephaly caused by Pqbp1-hypofunction in neural stem progenitor cells.2015

    • Author(s)
      Ito H, Shiwaku H, Yoshida C, Homma H, Luo H, Chen X, Fujita K, Musante L, Fischer U, Frints SG, Romano C, Ikeuchi Y, Shimamura T, Imoto S, Miyano S, Muramatsu SI, Kawauchi T, Hoshino M, Sudol M, Arumughan A, Wanker EE, Rich T, Schwartz C, Matsuzaki F, Bonni A, Kalscheuer VM, Okazawa H.
    • Journal Title

      Mol Psychiatry

      Volume: 20 Issue: 4 Pages: 459-71

    • DOI

      10.1038/mp.2014.69

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Unipotent, Atoh1+ progenitors maintain the Merkel cell population in embryonic and adult mice2015

    • Author(s)
      Wright MC, Reed-Geaghan EG, Bolock AM, Fujiyama T, Hoshino M, Maricich SM
    • Journal Title

      J Cell Biol

      Volume: 208 Issue: 3 Pages: 367-379

    • DOI

      10.1083/jcb.201407101

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cdk5 and its substrates, Dcx and p27kip1, regulate cytoplasmic dilation formation and nuclear elongation in migrating neurons.2014

    • Author(s)
      Nishimura YV, Shikanai M, Hoshino M, Ohshima T, Nabeshima Y, Mizutani K, Nagata K, Nakajima K and Kawauchi T
    • Journal Title

      Development

      Volume: 141 Issue: 18 Pages: 3540-3550

    • DOI

      10.1242/dev.111294

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Cytoskeletal regulation of AUTS2 in neuronal migration and neuritogenesis.2014

    • Author(s)
      Hori K., Nagai T., Shan W., Sakamoto A., Taya S., Hashimoto R., Hayashi T., Abe M., Yamazaki M., Nakao K., Nishioka T., Sakimura K., Yamada K., Kaibuchi K., Hoshino M.
    • Journal Title

      Cell Reports

      Volume: 9 Issue: 6 Pages: 2166-2179

    • DOI

      10.1016/j.celrep.2014.11.045

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genetic dissection of plexin signaling in vivo2014

    • 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

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [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

    • Related Report
      2013 Annual Research Report
    • 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

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Specification of spatial identities of cerebellar neuron progenitors by ptf1a and atoh1 for proper production of GABAergic and glutamatergic neurons2014

    • 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

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Infant calming responses during maternal carrying in humans and mice2013

    • 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

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Atoh1 directs hair cell differentiation and survival in the late embryonic mouse inner ear2013

    • 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

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Sharp Cadherin-6 gene expression boundary in the developing mouse cortical plate demarcates future functional areal border2013

    • 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

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A sharp Cadherin-6 gene expression boundary in the developing mouse cortical plate demarcates the future functional areal border.2013

    • Author(s)
      Terakawa, et al.
    • Journal Title

      Cereb Cortex

      Volume: (in press)

    • Related Report
      2012 Annual Research Report
    • 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

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neuronal subtype specification in the cerebellum and dorsal hindbrain2012

    • 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

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Cytoplasmic function of AUTS2 in neural network formation2015

    • Author(s)
      Hoshino M, Nagai T, Shen W, Sakamoto A, Taya S, Hashimoto R, Hayashi T, Abe M, Yamazaki M, Nakao K, Nishioka T, Sakimura K, Yamada K, Kaibuchi K, Hori K
    • Organizer
      Society for Neuroscience 45th annual meeting
    • Place of Presentation
      McCormick Place, Chicago, IL, USA
    • Year and Date
      2015-10-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Analysis of autism susceptibility candidate 2 gene during development2015

    • Author(s)
      Hoshino M, Hori K
    • Organizer
      Tohoku Forum for Creativity, Frontiers of Brain Science, “Development and Disease” symposium
    • Place of Presentation
      Tohoku University, Sendai, Japan
    • Year and Date
      2015-08-24
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 各種精神疾患とAUTS2遺伝子、そしてヒトの進化2015

    • Author(s)
      星野幹雄
    • Organizer
      平成27年度生理学研究所研究会「シナプスの構造構築と機能発現の分子基盤」
    • Place of Presentation
      生理学研究所, 岡崎
    • Year and Date
      2015-06-18
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Physiological and pathological analyses of an autism-related gene2015

    • Author(s)
      Hoshino M
    • Organizer
      EMBO Workshop on Cortical Development in Health and Disease
    • Place of Presentation
      Weizmann Institute of Science, Rehovot, Israel
    • Year and Date
      2015-04-26
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] イハラてんかんラットの解析2014

    • Author(s)
      星野幹雄
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Spatiotemporal regulation of cerebellar neural progenitor identities by transcription factors2014

    • Author(s)
      Hoshino M, Seto Y, Nakatani T, Kawaguchi Y, Ikenaka K, Takebayashi H, Ono Y, Yamada M
    • Organizer
      44th Annual Meeting of Society for Neuroscience
    • Place of Presentation
      Walter E. Washington Convention Center, Washington DC, USA
    • Year and Date
      2014-11-15 – 2014-11-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] Role of Meis1 in the cerebellar development2014

    • 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37回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] Analysis of the function of a psychiatric disorder-related gene during development2014

    • Author(s)
      Hoshino M, Hori K
    • Organizer
      12th Biennial Meeting of the Asian-Pacific-Society-for-Neurochemistry
    • Place of Presentation
      Howard Plaza Hotel Kaohsiung Taiwan, Kaohsiung, Taiwan
    • Year and Date
      2014-08-23 – 2014-08-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Spatiotemporal regulation of neural progenitor identities by transcription factors2014

    • Author(s)
      Hoshino M, Seto Y, Nakatani T, Kawaguchi Y, Ikenaka K, Takebayashi H, Ono Y, Yamada M
    • Organizer
      Joint Meeting of the 20th Biennial Meeting of the International Society for Developmental Neuroscience and the 5th Annual NeuroDevNet Brain Development Conference
    • Place of Presentation
      Hilton Motreal Bonaventure, Montreal, Canada
    • Year and Date
      2014-07-19 – 2014-07-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] Cytoskeletal regulation by AUTS2 in Neuronal migration and neuritogenesis2014

    • 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
    • Related Report
      2013 Annual Research Report
  • [Presentation] A genetic analysis of hypothalamic development and function by using Ptf1a-genetically modified mice2013

    • 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 Convention Center, San Diego, USA
    • Related Report
      2013 Annual Research Report
  • [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
    • Related Report
      2013 Annual Research Report
  • [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
    • Related Report
      2013 Annual Research Report
  • [Presentation] Sox9 controls oligodendrocyte differentiation in the cerebellum2013

    • 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
    • Related Report
      2013 Annual Research Report
  • [Presentation] Transcriptional regulation of the diversity of cerebellar GABA ergic 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
    • Related Report
      2012 Annual Research Report
  • [Presentation] Analysis of a rat model for human temporal lobe epilepsy2012

    • Author(s)
      Hoshino M
    • Organizer
      International Synapse Research Workshop
    • Place of Presentation
      愛知県岡崎市 自然科学研究(招待講演)
    • Related Report
      2012 Annual Research Report
  • [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
      ドイツ、マックスプランク研究所 リングパーク城
    • Related Report
      2012 Annual Research Report
  • [Book] Specification of cerebellar and precerebellar neurons; in "Handbook of the Cerebellum and Cerebellar Disorders"2012

    • Author(s)
      Hoshino, et al.
    • Total Pages
      13
    • Publisher
      Springer
    • Related Report
      2012 Annual Research Report
  • [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

    • Related Report
      2014 Annual Research Report
  • [Remarks]

    • URL

      http://www.ncnp.go.jp/nin/guide/r_diag/index.html

    • Related Report
      2012 Annual Research Report

URL: 

Published: 2012-04-24   Modified: 2019-07-29  

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