Regulation of neuronal differentiation and plasticity at posttranscriptional level

• Project/Area Number: 17024051
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Keio University
• Principal Investigator: OKANO Hideyuki Keio University, 医学部, 教授 (60160694)
• Co-Investigator(Kenkyū-buntansha): OKANO James Hirotaka 慶應義塾大学, 医学部, 准教授 (90338020)
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥31,600,000 (Direct Cost: ¥31,600,000); Fiscal Year 2009: ¥8,600,000 (Direct Cost: ¥8,600,000); Fiscal Year 2008: ¥7,900,000 (Direct Cost: ¥7,900,000); Fiscal Year 2007: ¥8,000,000 (Direct Cost: ¥8,000,000); Fiscal Year 2006: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2005: ¥3,500,000 (Direct Cost: ¥3,500,000)
• Keywords: 分子・細胞神経科学 / RNA結合タンパク質 / 神経幹細胞 / 翻訳調節 / 神経分化 / Hu Hzf Musashi / p21Cip1 / Hu / Hzf / 翻訳調 / Musashi / p21Cipl / IP3受容体 / RNA結合タンパク

Research Abstract

Neural RNA binding proteins play important roles in the processes of brain development and maturation. Here we show that Hu, Hzf and Musashi control neuronal differentiation, RNA transport and neural stem cell maintenance, respectively, through the post-transcriptional regulation of messenger RNA in the embryonic and adult brain.

Research Products

• [Journal Article] Kspot, a novel ubiquitin ligase, regulates synaptic activity. (2010)
  • Author(s): Tada H., Okano HJ., Takagi H., Shibata S., Matsumoto M., Yao I., Saiga T., Nakayama KI., Kashima H., Takahashi T, Setou M, Okano H.
  • Journal Title: J.Biol.Chem. 285(6) Pages: 3840-3849
  • NAID: 130005449632
  • Peer Reviewed
• [Journal Article] Stromal cell-secreted factors promote the survival of ES cell-derived early neural stem/progenitor cells via the activation of MAPK and PI3K-Akt pathways. (2010)
  • Author(s): Ishii S., Okada Y., Kadoya T., Matsuzaki Y., Shimazaki T., Okano H.
  • Journal Title: J.Neurosci.Res. 88(4) Pages: 722-773
  • Peer Reviewed
• [Journal Article] Musashi1 as a marker of reactive astrocytes after transient focal brain ischemia. (2009)
  • Author(s): Oki K, Kaneko N, Kanki H Sa wamoto K, Okano H.
  • Journal Title: Neurosci. Res. 66(4) Pages: 390-5
  • Peer Reviewed
• [Journal Article] Musashi-1, an RNA-binding protein, is indispensable for survival of photoreceptors. (2009)
  • Author(s): Susaki K, Kaneko J, Yamano Y, Nakamura K, In ami W, Yoshikawa T, Ozawa Y, Shibata S, Matsuzaki O, Okano H, Chiba C
  • Journal Title: Experimental eye research 88 Pages: 47-55
  • Peer Reviewed
• [Journal Article] Cell types to order : Temporal specification of CNS stem cells. (2009)
  • Author(s): Okano H., Temple S.
  • Journal Title: Current Opinion in Neurobiology 19 Pages: 112-119
  • Peer Reviewed
• [Journal Article] Precursor maintenance and GABAergic neuronal differentiation mediated by the PDK1-Akt pathway in mouse telencephalon. (2009)
  • Author(s): Oishi K., Watatani K., Yoshimatsu T., Masuyama N., Nakajima K., Okano H., Guillemot F., Alessi DR., Gotoh Y.
  • Journal Title: Proc.Natl.Acad.Sci.USA 106(31) Pages: 13064-13069
  • Peer Reviewed
• [Journal Article] Cyclic alopecia caused by the disruption of Sox21- mediated hair shaft cuticle differentiation. (2009)
  • Author(s): Kiso M., Tanaka S., Saba R., Matsuda S., Shimizu A., Ohyama M., James-Okano H., Shiroishi T., Okano H., Saga Y.
  • Journal Title: Proc.Natl.Acad.Sci.USA 106(23) Pages: 9292-9297
  • Peer Reviewed
• [Journal Article] Fbxo45 forms a novel ubiquitin ligase complex and is required for neuronal development. (2009)
  • Author(s): Saiga T., Fukuda T., Matsumoto M., Tada H., Okano HJ., Okano H., Nakayama KI.
  • Journal Title: Mol.Cell Biol. 29(13) Pages: 3529-3543
  • Peer Reviewed
• [Journal Article] e ural RNA-binding protein Musashi1 Inhibits Translation Initiation by Competing with eIF4G for PABP. (2008)
  • Author(s): Kawahara H, Imai T, Imataka H, Okano H.
  • Journal Title: J. Cell Biol. 181 Pages: 639-653
  • Peer Reviewed
• [Journal Article] Hzf regulates adipogenesis through translational control of C/EBPalpha. (2008)
  • Author(s): Kawagishi H, Wakoh T, Uno H, Maruyama M, Mo riya A, Morikawa S, Okano H, Sherr CJ, Takagi M, Sugimoto M
  • Journal Title: The EMBO journal 27 Pages: 1481-90
  • Peer Reviewed
• [Journal Article] Re quirement for COUP-TFI and II in the temporal specification of neural stem cells in CNS development. (2008)
  • Author(s): Naka H, Nakamura S, Shimazaki T, Okano H
  • Journal Title: Nature neuroscience 11 Pages: 1014-23
  • Peer Reviewed
• [Journal Article] (2008)
  • Author(s): Kawahara H, Yano M, Imai T, Akamatsu W, Okano HJ, Okano H, Kawahara H, Yano M, Imai T, Akamatsu W, Okano HJ, Okano H
  • Journal Title: Kerala, India
  • Peer Reviewed
• [Journal Article] Requirement for COUP-TFI and II in the temporal specification of neura I stem cells in central nervous system development (2008)
  • Author(s): Naka H., Nakamura S., Shimazaki T., Okano H.
  • Journal Title: Nature Neurosci 11(9) Pages: 1014-1023
  • Peer Reviewed
• [Journal Article] Spatio-temporal recapitulation of central nervous system development by ES cell-derived neural stem/progenitor cells (2008)
  • Author(s): Okada Y., Matsumoto A., Shimazaki T., Enoki R., Koizumi A., Ishii S., Itoyama Y., Sobue G., Okano H.
  • Journal Title: Stem Cells 26 Pages: 3086-3098
  • Peer Reviewed
• [Journal Article] In vivo imaging in humanized mice (2008)
  • Author(s): Masuda H., Okano HJ., Maruya ma T., Yoshimura Y., Okano H., Matsuzaki Y
  • Journal Title: Curr Top Microbiol Immunol 324 Pages: 179-196
  • Peer Reviewed
• [Journal Article] Hzf regulates adipogenesis through translational control of C/EBPa (2008)
  • Author(s): Kawagishi H., Wakoh T., Uno H Maruyama M., Moriya A., Morikawa S., Okano H., Sherr C J., Takagi M., Sugimoto M.
  • Journal Title: EMBO J 27 Pages: 1481-1490
  • Peer Reviewed
• [Journal Article] Stage/Cell cycle phase specific nestin gene expression coordinated with the morphological alteration of embryonic cortical neural progenitor cells (2008)
  • Author(s): Sunabori T., Tokunaga A., Nagai T., Sawamoto K., Okabe M., Miyawaki A., Matsuzaki Y., Miyata T., Okano H
  • Journal Title: J. Cell Sci 121 Pages: 1204-1212
  • Peer Reviewed
• [Journal Article] Neural RNA-binding protein Musashil inhibits translation initiation bycompeting with eIF4G for PABP. (2008)
  • Author(s): Kawahara, N., et al.
  • Journal Title: J.Cell.Biol. (in press)
  • Peer Reviewed
• [Journal Article] Expression of neural RNA binding protein, Musashi1 in pediatric brain tumors. (2007)
  • Author(s): Nakano A, Kanemura Y, Mori K, Kodama E, Ya mamoto A, Sakamoto H, Nakamura Y, Okano H, Yamasaki M, Arita N.
  • Journal Title: Pediatric Neurosurgery 43 Pages: 279-283
  • Peer Reviewed
• [Journal Article] Coordinated Expression of HuD and GAP-43 in Hippocampal Dentate Granule Cells During Developmental and Adult Plasticity. (2007)
  • Author(s): Bolognani F, Tanner DC, Nixon S, Okano HJ, Okano H, Perrone-Bizzozero NI.
  • Journal Title: eurochem Res. 32 Pages: 2142-2151
  • Peer Reviewed
• [Journal Article] Impaired Motor Functions in Mice Lacking the RNA-binding Protein Hzf. (2007)
  • Author(s): Iijima T, Ogura H, Takatsuki K, Shigenori Ka wahara S, Wakabayashi K, Nakayama D, Fujioka M, Kimura Y, Bernstein A, Okano HJ, Kirino Y, Okano H.
  • Journal Title: Neurosci Res 58 Pages: 183-189
  • NAID: 10024415208
  • Peer Reviewed
• [Journal Article] Musashi-1 expression in postnatal mouse olfactory epithelium. (2007)
  • Author(s): Watanabe K, Kondo K, Takeuchi N, Okano H, Yam asoba T
  • Journal Title: Neuroreort 18 Pages: 641-644
  • Peer Reviewed
• [Journal Article] Impaired Motor Functions in Mice Lacking the RNA-biading Protein Hzf. (2007)
  • Author(s): Iijima, T., et al.
  • Journal Title: Neurosci Res. 58 Pages: 183-189
  • Peer Reviewed
• [Journal Article] Coordinated Expression of HuD and GAP-43 in Hippocampal Dentate Granule Cells During Developmental and Adult Plasticity. (2007)
  • Author(s): Bolognani, F., et al.
  • Journal Title: Neurochem Res. 32 Pages: 2142-2151
  • Peer Reviewed
• [Journal Article] A carbohydrate-binding protein, Galectin-1, promotes proliferation of adult neural stem cells. (2006)
  • Author(s): Sakaguchi M, Shingo T, S himazaki T, Okano HJ, Shiwa M, Ishibashi S, Oguro H, Ninomiya M, Kadoya T, Horie H, Shibuya A, Mizusawa H, Poirier F, Nakauchi H, Sawamoto K, Okano H.
  • Journal Title: Proc Natl Acad Sci USA. 103(18) Pages: 7112-7117
  • Peer Reviewed
• [Journal Article] Musashi1 antigen expression in human fetal germinal matrix development. (2006)
  • Author(s): Chan C, Moore BE, Cotman CW, Okano H, Tavares R, Hovanesian V, Pinar H, Johanson CE, Svendsen CN, Stopa EG
  • Journal Title: Exp Neurol. 201 Pages: 515-518
  • Peer Reviewed
• [Journal Article] A carbohydrate binding protein, Galectin-1, promotes proliferation of adult neural stem cells (2006)
  • Author(s): Sakaguchi M. et al.
  • Journal Title: Proc. Natl. Acad. Sci. USA. 103 Pages: 7112-7117
• [Journal Article] Involvement of Hu and heterogeneous nuclear ribonucleoprotein K in neuronal differentiation through p21 mRNA post-transcriptional regulation. (2005)
  • Author(s): Yano M, Okano HJ, Oka no H
  • Journal Title: The Journal of biological chemistry 280 Pages: 12690-12699
  • Peer Reviewed
• [Journal Article] The RNA-binding protein HuD regulates neuronal cell identity and maturation. (2005)
  • Author(s): Akamatsu W, Fujihara H, Mitsuhashi T, Yano M, Shibata S, Hayakawa Y, Okano HJ, Sakakibara S, Takano H, Takano T, Takahashi T, Noda T, Okano H
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America 102 Pages: 4625-30
  • Peer Reviewed
• [Journal Article] Function of RNA-binding protein Musashi-1 in stem cells. (2005)
  • Author(s): Okano H, Kawahara H, Toriya M, Nakao K, Shibata S, Imai T
  • Journal Title: Experimental cell research 306 Pages: 349-56
  • Peer Reviewed
• [Journal Article] Hzf protein regulates dendritic localization and BDNF-induced translation of type 1 inositol 1, 4, 5-trisphosphate receptor mRNA. (2005)
  • Author(s): Iijima T, Imai T, Kimura Y, Bernstein A, Okano HJ, Yuzaki M, Okano H
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America 102 Pages: 17190-5
  • Peer Reviewed
• [Journal Article] Involvement of Hu and hnRNP K in neuronal differentiation through p21 mRNA post-transcriptional regulation (2005)
  • Author(s): Yano M.et al.
  • Journal Title: J.Biol.Chem 280 Pages: 12690-12699
• [Journal Article] RNA-binding protein HuD regulates neuronal cell identity and maturation. (2005)
  • Author(s): Akamatsu W. et al.
  • Journal Title: Proc Natl Acad Sci USA. 102 Pages: 4625-4630
• [Journal Article] Hzf Protein Regulates Dendritic Localization and BDNF-induced Translation of Type 1 Inositol 1,4,5-Trisphosphate Receptor mRNA. (2005)
  • Author(s): Iijima T. et al.
  • Journal Title: Proc Natl Acad Sci USA. 102 Pages: 17190-17195
• [Journal Article] Impaired Motor Functions in Mice Lacking the RNA-binding Protein Hzf
  • Author(s): Iijima T. et al.
  • Journal Title: Neurosci Res. (In press)
• [Presentation] Sensory neural network formation with RNA binding protein Musashi-2 deficient mice. (2009)
  • Author(s): Shinsuke Shibata
  • Organizer: 36th International Congress Of Physiological Sciences (IUPS2009)
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2009-07-30
• [Presentation] Roles of RNA Binding Protein Hu in Developing and Mature Neurons. (2009)
  • Author(s): Hirotaka James Okano
  • Organizer: 36th Intemational Congress Of Physiological Sciences (IUPS2009)
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2009-07-30
• [Presentation] Axonal degeneration in HuC-deficient Cerebellum. (2009)
  • Author(s): Kyoko Kakumoto
  • Organizer: 36th International Congress Of Physiological Sciences (IUPS2009)
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2009-07-30
• [Presentation] Roles of RN A Binding Protein Hu in Developing and Mature Neurons. (2009)
  • Author(s): Okano HJ.
  • Organizer: 36th International Congress Of Physiological Sciences (IUPS2009)
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2009-07-03
• [Presentation] Neural differentiation of pluripotent stem cells based therapy for spinal cord injury (2008)
  • Author(s): Okano H.
  • Organizer: the National Centre for Adult Stem Cell Research conference, Adult Stem Cells - Biology and Clinical Applications Meeting
  • Place of Presentation: Griffith University, Queensland, Australia
  • Year and Date: 2008-11-27
• [Presentation] Neural differentiation of pluripotent stem cells based therapy for spinal cord injury, the National Centre for Adult Stem Cell Research conference (2008)
  • Author(s): H. Okano
  • Organizer: Adult Stem Cells - Biology and Clinical Applications Meeting
  • Place of Presentation: Griffith University, Queensland, Australia
  • Year and Date: 2008-11-27
• [Presentation] Neural differentiation of pluripotent stem cells based therapy for spinal cord injury (2008)
  • Author(s): Hideyuki Okano
  • Organizer: the National Centre for Adult Stem Cell Research conference, Adult Stem Cells-Biology and Clinical Applications Meeting
  • Place of Presentation: Griffith University, Que ensland, Australia
  • Year and Date: 2008-11-27
• [Presentation] Regeneration of the damaged CNS using stem cells (2008)
  • Author(s): Okano H.
  • Organizer: Neural Stem Cells & Regenarative Neuroscience Workshop
  • Place of Presentation: Scientia Building, UNSW, Sydney Australia
  • Year and Date: 2008-09-06
• [Presentation] Neural differentiation and cell therapy using pluripotent stem cells (2008)
  • Author(s): Okano H.
  • Organizer: 2nd Symposium on Brain and Mind Research in the Asia / Pacific (BMAP)
  • Place of Presentation: the Matrix, Biopolis, Singapore.
  • Year and Date: 2008-09-03
• [Presentation] Neural differentiation and cell therapy using pluripotent stem cells (2008)
  • Author(s): Hideyuki Okano
  • Organizer: 2^<nd> Symposium on Brain and Mind Research in the Asia / Pacific (BMAP)
  • Place of Presentation: the Matrix, Biopolis, Si ngapore
  • Year and Date: 2008-09-03
• [Presentation] Strategies for the regeneration of damaged CNS (2008)
  • Author(s): Okano H.
  • Organizer: The 17th Biennial Meeting of the International Society for Developmental Neuroscience
  • Place of Presentation: Asilomar, CA, U.S.A.
  • Year and Date: 2008-06-03
• [Presentation] Strategies for the regeneration of damaged CNS (2008)
  • Author(s): Hideyuki Okano
  • Organizer: The 17^<th> Biennial Meeting of the International Society for Developmental Neuroscience
  • Place of Presentation: Asilomar, CA, U.S.A.
  • Year and Date: 2008-06-03
• [Presentation] Molecular Identification of Neural Stem Cell Self-renewing Factor (2007)
  • Author(s): Okano, H.
  • Organizer: 4th Annual Christopher Reeve "HOT TOPICS" IN STEM CELL BIOLOGY, Satellite Symposium at the 2007 Annual Meeting of the Society For Nuroscience
  • Place of Presentation: San Diego, USA.
  • Year and Date: 2007-11-15
• [Presentation] Neural Stem Cells: their involvement in adult neurogenesis and CNS-repair (2007)
  • Author(s): Okano, H.
  • Organizer: 8th World Congress on Inflammation
  • Place of Presentation: Copenhagen, Denmark.
• [Presentation] Neural Stem Cells: their involvement in adult neurogenesis and CNS-repair (2007)
  • Author(s): Okano, H.
  • Organizer: Stem Cells and CNS Regeneration (Symposium by biosymposia, Inc. )
  • Place of Presentation: Boston, USA.
• [Presentation] Neural Stem Cells: their involvement in adult neurogenesis and CNS-repair. (2007)
  • Author(s): Okano. H.
  • Organizer: 8th World Congress on Inflammation
  • Place of Presentation: Copenhagen, Denmark.
• [Presentation] A rol of neuronal RNA binding protein Hu and NF45/90 in the nervous system. (2007)
  • Author(s): Okano, HJ., Igarashi, M., Yano, M.& Okano, H.
  • Organizer: 2007 Annual Meeting of the Society For Nuroscience
  • Place of Presentation: San Diego, USA.
• [Book] Functions of neural RNA-binding proteins Musashi and Hu in stem cells and neuronal differentiation. RNA Binding Proteins in Development and Disease. (Edited by Robert B. Denman) (2008)
  • Author(s): Kawahara, H., Yano, M., Imai, T., Akamatsu, W., Okano, HJ., Okano, H.
  • Publisher: Research Signpost, Kerala
• [Book] Functions of neural RNA-binding proteins Musashi and Hu in stem cells and neuronal differentiation. (2008)
  • Author(s): Kawahara, H., et al.
  • Publisher: RNA Binding Proteins in Development and Disease. (Edited by Robert B. Denman), Research Signpost, Kerala, India.
• [Book] RNA Binding Proteins in Development and Disease
  • Author(s): Kawahara H. et al.
  • Publisher: Research Signpost(In press)
• [Remarks]
  • URL: http://www.okano-lab.com/
• [Patent(Industrial Property Rights)] 神経幹細胞の増殖抑制剤 (2010)
  • Inventor(s): 岡野栄之, 他
  • Industrial Property Rights Holder: 学校法人慶應義塾、独立行政法人産業技術総合研究所
  • Acquisition Date: 2010-02-16
• [Patent(Industrial Property Rights)] 神経幹細胞の増殖抑制剤 (2010)
  • Inventor(s): 岡野栄之、坂口昌徳、澤本和延、平林淳
  • Industrial Property Rights Holder: 学校法人慶應義塾,(独)産業技術総合研究所
  • Acquisition Date: 2010-02-16
• [Patent(Industrial Property Rights)] 神経損傷治療剤及び神経損傷治療方法 (2008)
  • Inventor(s): 岡野栄之, 他
  • Industrial Property Rights Holder: 学校法人慶應義塾、国立大学法人京都大学
  • Industrial Property Number: 2008-005844
  • Filing Date: 2008-03-07
• [Patent(Industrial Property Rights)] 脊髄損傷治療藥剤 (2008)
  • Inventor(s): 岡野栄之, 他
  • Industrial Property Rights Holder: 学校法人慶應義塾、国立大学法人大阪大学、クリングルファーマ株式会社
  • Filing Date: 2008-02-08
• [Patent(Industrial Property Rights)] 神経損傷治療剤及び神経損傷治療方法 (2008)
  • Inventor(s): 岡野栄之、中村雅也、辻収彦、山中伸弥、三浦恭子
  • Industrial Property Rights Holder: 学校法人慶応義塾大学、国立大学法人京都大学
  • Filing Date: 2008-06-30
  • Overseas
• [Patent(Industrial Property Rights)] 神経損傷治療剤及び神経損傷治療方法 (2008)
  • Inventor(s): (慶應)岡野栄之、中村雅也、辻収彦(共願先), 山中伸弥、三浦恭子
  • Industrial Property Rights Holder: 学校法人慶應義塾、国立大学法人京都大学
  • Industrial Property Number: 2008-058447
  • Filing Date: 2008-03-07
• [Patent(Industrial Property Rights)] METHOD FOR TREATING THENEURAL INJURY (2008)
  • Inventor(s): (慶應)岡野栄之、中村雅也、辻収彦(共願先), 山中伸弥、三浦恭子
  • Industrial Property Rights Holder: 学校法人慶應義塾、国立大学法人京都大学
  • Filing Date: 2008-02-15
  • Overseas
• [Patent(Industrial Property Rights)] AGENT FOR TREATMENT OF NEURAL INJURY ADN METHOD OF THE SAME (2008)
  • Inventor(s): (慶應)岡野栄之、中村雅也、辻収彦(共願先), 山中伸弥、三浦恭子
  • Industrial Property Rights Holder: 学校法人慶應義塾、国立大学法人京都大学
  • Filing Date: 2008-03-07
  • Overseas