The significance of adult neurogenesis

2011 Fiscal Year Final Research Report

• Project/Area Number: 21240028
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neuroscience in general
• Research Institution: Kyoto University
• Principal Investigator: KAGEYA Maryoichiro 京都大学, ウイルス研究所, 教授 (80224369)
• Project Period (FY): 2009 – 2011
• Keywords: 成体脳 / ニューロン新生 / 神経幹細胞 / 海馬 / 歯状回 / 嗅球

Research Abstract

To understand the significance of adult neurogenesis, we genetically ablated newly born neurons in the adult mouse brain. Mutant mice showed defects in predator odor avoidance. Furthermore, mutant males displayed deficits in male-male aggression and sexual behaviors toward females, while mutant females displayed deficits in fertility and nurturing. These results suggest that adult neurogenesis plays an essential role in predator avoidance and gender-specific responses that are olfactory-dependent and innately programmed.

Research Products

• [Journal Article] Mind bomb 1 is required for pancreatic b-cell formation (2012)
  • Author(s): Horn, S., Kobberup, S., Jorgensen. M. C., Kalisz, M., Klein, T., Kageyama, R., Gegg, M., Lickert, H., Lindner, J., Magnuson, M. A., Kong, Y.-Y, Serup, P., Ahnfelt-Ronne, J., Jensen, J. N.
  • Journal Title: Proc. Natl. Acad. Sci
• [Journal Article] Light-induced silencing of neural activity in Rosa26 knock-in mice conditionally expressing the microbial halorhodopsin eNpHR2. 0. (2012)
  • Author(s): Imayoshi, I., Tabuchi, S., Hirano, K., Sakamoto, M., Kitano, S., Miyachi, H., Yamanaka, A., and Kageyama, R.
  • Journal Title: Res. in press
• [Journal Article] In vivo evaluation of PhiC31 recombinase activity in transgenic mice (2012)
  • Author(s): Imayoshi, I., Hirano, K., Kitano, S., Mitachi, H., and Kageyama, R.
  • Journal Title: Res. in press
• [Journal Article] A multifunctional teal-fluorescent Rosa26 reporter mouse line for Cre-and Flp-mediated recombination. (2012)
  • Author(s): Imayoshi, I., Hirano, K., Sakamoto, M., Miyoshi, G., Imura, T., Kitano, S., Mitachi, H., and Kageyama, R.
  • Journal Title: Res. in press Volume: 73 Pages: 85-91
  • DOI: DOI:10.1016/j.neures.2012.03.008
• [Journal Article] A mechanism for gene-environment interaction in the etiology of congenital scoliosis (2012)
  • Author(s): Sparrow, D. B., Chapman, G., Smith, A. J., Mattar, M. Z., Major, J. A., O' Reilly, V. C., Saga, Y., Zackai, E. H., Dormans, J. P., Alman, B. A., McGregor, L., Kageyama, R., Kusumi, K., and Dunwoodie, S. L.
  • Journal Title: Cell Volume: 149 Pages: 295-306
  • DOI: DOI:10.1016/j.ce11.2012.02.054
• [Journal Article] The role of Hes genes in intestinal development, homeostasis and tumor formation (2012)
  • Author(s): Ueo, T., Imayoshi, I., Kobayashi, T., Ohtsuka, T., Seno, H., Nakase, H., Chiba, T., and Kageyama, R.
  • Journal Title: Development Volume: 139 Pages: 1071-1082
  • DOI: DOI:10.1242/dev.069070
• [Journal Article] Notchl mediates visfatin-induced FGF-2 upregulation and endothelial angiogenesis. (2011)
  • Author(s): Bae, Y.-H., Park, H.-J., Kim, S. R., Kim, J. Y., Kang, Y. Kim, J. A., Wee, H.-J., Kageyama, R., Jung, J. S., Bae, M.-K., and Bae, S.-K.
  • Journal Title: Cardiovasc. Res. Volume: 89 Pages: 436-445
  • DOI: DOI:10.1093/cvr/cvq276
• [Journal Article] Fbxw7-dependent degradation of Notch is required for control of syemness and neuronal-glial differentiation in neural stem cells (2011)
  • Author(s): Matsumoto, A., Onoyama, I., Sunabori, T., Kageyama, R., Okano, H., and Nakayama, K. I.
  • Journal Title: J. Biol. Chem Volume: 286 Pages: 13754-13764
  • DOI: DOI:10.1074/jbc.M110.194936
• [Journal Article] Gene expression profiling of neural stem cells and identification of regulators of neural differentiation during cortical development (2011)
  • Author(s): Ohtsuka, T., Shimojo, H., Matsunaga, M., Watanabe, N., Kometani, K., Minato, N., and Kageyama, R.
  • Journal Title: Stem Cells Volume: 29 Pages: 1817-1828
  • DOI: DOI:10.1002/stem.731
• [Journal Article] Notch-Hes 1 pathway induces IL-17-producing gd T cells (2011)
  • Author(s): Shibata, K., Yamada, H., Sato, T? Dejima, S., Nakamura, M., Ikawa, T., Hara, H., Yamasaki, S., Kageyama, R., Iwakura, Y., Kawamoto, H., Toh, H., and Yoshikai, Y.
  • Journal Title: Blood Volume: 118 Pages: 586-593
  • DOI: DOI:10.1182/blood-2011-02-334995
• [Journal Article] Different types of oscillations in Notch and Fgf signaling regulate the spatiotemporal periodicity of somitogenesis (2011)
  • Author(s): Niwa, Y., Shimojo, H., Isomura, A., Gonzalez, A., Miyachi, H., and Kageyama, R.
  • Journal Title: Genes & Dev Volume: 25 Pages: 1115-1120
  • DOI: DOI:10.1101/gad.2035311
• [Journal Article] Continuous neurogenesis in the adult forebrain is required for innate olfactory responses. (2011)
  • Author(s): Sakamoto, M., Imayoshi, I., Ohtsuka, T., Yamaguchi, M., Mori, K., and Kageyama, R.
  • Journal Title: Natl. Acad. Sci. USA Volume: 108 Pages: 8479-8484
  • DOI: DOI:10.1073/pnas.1018782108
• [Journal Article] Cooperative functions of Hes/Hey genes in auditory hair cell and supporting cell development. (2011)
  • Author(s): Tateya, T., Imayoshi, I., Tateya, I., Ito, J., and Kageyama, R.
  • Journal Title: Biol Volume: 352 Pages: 329-340
  • DOI: DOI:10.1016/j.ydbio.2011.01.038
• [Journal Article] Intronic delay is essential for oscillatory expression in the segmentation clock. (2011)
  • Author(s): Takashima, Y., Ohtsuka, T., Gonzalez, A., Miyachi, H., and Kageyama, R.
  • Journal Title: Natl. Acad. Sci. USA Volume: 108 Pages: 3300-3305
  • DOI: DOI:10.1073/pnas.1014418108
• [Journal Article] Six 1 is indispensable for production of functional apical and basal progenitors during olfactory epithelial development. (2010)
  • Author(s): Ikeda, K., Kageyama, R., Suzuki, Y., and Kawakami, K.
  • Journal Title: Int. J. Dev. Biol Volume: 54 Pages: 1453-1464
  • DOI: DOI:10.1387/ijdb.093041ki
• [Journal Article] Hesl regulates embryonic stem cell differentiation by suppressing Notch signaling (2010)
  • Author(s): Kobayashi, T. and Kageyama, R.
  • Journal Title: Genes to Cells Volume: 15 Pages: 689-698
  • DOI: DOI:10.1111/j.1365-2443.2010.01413.x
• [Journal Article] HES1 and HESS are dispensable for cartilage and endochondral bone formation (2010)
  • Author(s): Karlsson, C., Brantsing, C., Kageyama, R., and Lindahl, A.
  • Journal Title: Cells Tissue Organs Volume: 192 Pages: 17-27
  • DOI: DOI:10.1159/000280416
• [Journal Article] Maximizing functional photoreceptor differentiation from adult human retinal stem cells. (2010)
  • Author(s): Inoue, T., Coles, B., Dorval, K., Bremner, R., Bessho, Y., Kageyama, R., Hino, S., Matsuoka, M., Craft, C., McInnes, R., Temblay, F., Prusky, G., Tano, Y., and van der Kooy, D.
  • Journal Title: Stem Cells Volume: 28 Pages: 489-500
  • DOI: DOI:10.1002/stem.27
• [Journal Article] Zinc-finger genes Fezfl and Fezfl control neuronal differentiation by repressing Hes5 expression in forebrain (2010)
  • Author(s): Shimizu, T., Nakazawa, M., Kani, S., Bae, Y.-K., Shimizu, T., Kageyama, R., and Hibi, M.
  • Journal Title: Development Volume: 137 Pages: 1875-1885
  • DOI: DOI:10.1242/dev.047167
• [Journal Article] Essential roles of Notch signaling in maintenance of neural stem cells in the developing and adult brains. (2010)
  • Author(s): Imayoshi, I., Sakamoto, M., Yamaguchi, M., Mori, K., and Kageyama, R.
  • Journal Title: J. Neurosci Volume: 30 Pages: 3489-3498
  • DOI: DOI:10.1523/JNEUROSCI.4987-09.2010
• [Journal Article] Spatio-temporal pattern in somitogenesis : a non-Turing scenario with wave propagation. (2009)
  • Author(s): Nagahara, H., Ma, Y., Takenaka, Y., Kageyama, R., and Yoshikawa, K.
  • Journal Title: Physical Rev. E Volume: 80 Pages: 0219106(1-7)
  • DOI: DOI:10.1103/PhysRevE.80.021906
• [Journal Article] The first Hesl dimer inhibitors from natural products. (2009)
  • Author(s): Arai, M., Masada, A., Ohtsuka, T., Kageyama, R., and Ishibashi, M.
  • Journal Title: Chemistry Letters Volume: 19 Pages: 5778-5781
  • DOI: DOI:10.1016/j.bmc1.2009.07.146
• [Journal Article] Notch-Hesl pathway contributes to the cochlear prosensory formation potentially through the transcriptional down-regulation of p27(Kip1) (2009)
  • Author(s): Murata, J., Ohtsuka, T., Tokunaga, A., Nishiike, S., Inohara, H., Okano, H., and Kageyama, R.
  • Journal Title: J. Neurosci. Res Volume: 87 Pages: 3521-3534
  • DOI: DOI:10.1002/jnr.22169
• [Journal Article] The cyclic gene Hesl contributes to diverse differentiation responses of embryonic stem cells (2009)
  • Author(s): Kobayashi, T., Mizuno, H., Imayoshi, I., Furusawa, C., Shirahige, K., and Kageyama, R.
  • Journal Title: Genes & Dev Volume: 223 Pages: 1870-1875
  • DOI: DOI:10.1101/gad.1823109
• [Journal Article] Hopf Bifurcation in the Presomitic Mesoderm during the Mouse Segmentation (2009)
  • Author(s): Gonzalez, A., and Kageyama, R.
  • Journal Title: J. Theor. Biol Volume: 259 Pages: 176-189
  • DOI: DOI:10.1016/j.jtbi.2009.02.00HM94ft)
• [Presentation] Spatiotemporal regulation of somitogenesis by the oscillator networks of the segmentation clock. (2011)
  • Author(s): Kageyama, R.
  • Organizer: Annual Meeting of American Society for Cell Biology
  • Place of Presentation: Denver, USA
  • Year and Date: 20110109-14
• [Presentation] The role of Notch signaling in proliferation and differentiation of neural stem cells (2010)
  • Author(s): Kageyama, R.
  • Organizer: Fondation Des Treilles
  • Place of Presentation: France
  • Year and Date: 20101003-1006
• [Presentation] TThe oscillator networks in the somite segmentation clock (2010)
  • Author(s): Kageyama, R.
  • Organizer: The Notch Meeting V
  • Place of Presentation: Athens, Greece
  • Year and Date: 20100926-30
• [Presentation] The significance and mechanism of ultradian oscillations in somite segmentation and other biological events (2010)
  • Author(s): Kageyama, R.
  • Organizer: International Workshop on Timing and Dynamics in Biological SystemsJDresden
  • Place of Presentation: Germany
  • Year and Date: 20100926-30
• [Presentation] The role of Notch signaling in embryonic and adult neural stem cells (2010)
  • Author(s): Kageyama, R.
  • Organizer: The Company of Biologists Workshops
  • Place of Presentation: West Sussex, UK
  • Year and Date: 20100920-24
• [Presentation] The role of Notch signaling in embryonic and adult neural stem cells (2010)
  • Author(s): Kageyama, R.
  • Organizer: Perspectives of Stem Cells
  • Place of Presentation: Sao Paulo, Brazil
  • Year and Date: 20100920-24
• [Presentation] Essential roles of Notch signaling in embryonic and adult neural stem cells (2010)
  • Author(s): Kageyama, R.
  • Organizer: 23^<rd> Biennial Meeting of the International Society for Neurochemistry
  • Place of Presentation: Athens, Greece
  • Year and Date: 20100617-19
• [Presentation] The role of Notch signaling in embryonic and adult neural stem cells (2010)
  • Author(s): Kageyama, R.
  • Organizer: ENP Neural Stem Cell Meeting
  • Place of Presentation: Abbaye des Vaux de Cernay, France
  • Year and Date: 20100617-19
• [Presentation] Ultradian oscillations in somite segmentation and other biological events (2010)
  • Author(s): Kageyama, R.
  • Organizer: The 6^<th> bHLH Symposium
  • Place of Presentation: Shanghai, China
  • Year and Date: 20100606-09
• [Presentation] The role of Notch signaling in embryonic and adult neurogenesis (2010)
  • Author(s): Kageyama, R.
  • Organizer: 18^<th> Biennial Meeting of the International Society for Developmental Neuroscience
  • Place of Presentation: Lisbon, Portugal
  • Year and Date: 20100606-09
• [Presentation] The role of Notch signling in proliferation and differentiation of adult neural stem cells (2009)
  • Author(s): Kageyama, R.
  • Organizer: Joint Japan-Australia-New Zealand Symposium-Building a Functional BrainJAuckland
  • Place of Presentation: New Zealand
  • Year and Date: 20090927-1001
• [Presentation] The role of Hes1 oscillations in regulation of stem progenitor cells (2009)
  • Author(s): Kageyama, R.
  • Organizer: The Notch Meeting V
  • Place of Presentation: Athens, Greece
  • Year and Date: 20090927-1001
• [Presentation] Functional significance of neurogenesis in the olfactory bulb. (2009)
  • Author(s): Kageyama, R.
  • Organizer: Keystone Symposium-Adult Neurogenesis
  • Place of Presentation: Taos, USA
  • Year and Date: 20090617-19
• [Presentation] Ultradian oscillators in somite segmentation and other biological events (2009)
  • Author(s): Kageyama, R.
  • Organizer: Symposium on Developmental Biology
  • Place of Presentation: London, UK
  • Year and Date: 20090617-19
• [Presentation] Essential roles of Notch signaling in embryonic and adult neural stem cells (2009)
  • Author(s): Kageyama, R.
  • Organizer: Notch and Stem Cells
  • Place of Presentation: London, UK
  • Year and Date: 20090507-08
• [Presentation] The role of Hes1 in proliferation and differentiation of neural stem cells (2009)
  • Author(s): Kageyama, R.
  • Organizer: EMBO Workshop/5^<th> International Symposium on bHLH transcription factors
  • Place of Presentation: London, UK
  • Year and Date: 20090507-08
• [Presentation] Ultradian oscillators in somite segmentation and other biological events (2009)
  • Author(s): Kageyama, R.
  • Organizer: 8^<th> International Conference on Information Processing in Cells and Tissues
  • Place of Presentation: Ascona, Switzerland
  • Year and Date: 20090405-09
• [Book] ltradian oscillations in Notch signaling regulate dynamic biological events (2010)
  • Author(s): Kageyama, R., Niwa, Y., Shimojo, H., Kobayashi, T., and Ohtsuka, T.
  • Total Pages: 311-331
  • Publisher: Curr. Top. Dev. Biol
• [Book] 2010 YearBook of Science & Technology (2010)
  • Author(s): Kageyama, R., Niwa, Y., and Shimojo, H.
  • Total Pages: 102-104
  • Publisher: McGraw-Hill
• [Book] In Systems Biology(Eds, S. Nakanishi, R. Kageyama, and D. Watanabe) (2009)
  • Author(s): Niwa, Y., Shimojo, H., and Kageyama, R.
  • Total Pages: 199-207
  • Publisher: Springer
• [Remarks]
  • URL: http://www.virus.kyoto-u.acjp/Lab/Kageyama/index.html
• [Remarks] マスコミ報(1)道振動遺伝子Hes1が胚性幹細胞の多様な分化応答に寄与:朝日新聞(平成21年8月15日夕刊8面)、京都新聞(8月15日夕刊8面)、日本経済新聞(8.月16日34面)、毎日新聞(8月15日夕刊7面)および読売新聞(8月15日夕刊2面)
• [Remarks] (2)胚性幹細胞におけるHes1オシレーションの意義: NHK教育テレビサイエンスZERO平成22年4月3日
• [Remarks] (3)成体脳ニューロン新生と匂い情報処理: NHK教育テレビサイエンスZERO平成22年6月26日
• [Remarks] (4)分節時計遺伝子がリズムを刻むにはイントロンによる発現の遅れが必須:朝日新聞(平成23年2月8日)、京都新聞(2月8日朝刊)
• [Remarks] (5)成体脳におけるニューロン新生は先天的な匂い応答に必要である。:京都新聞(平成23年5月3日21面)
• [Patent(Industrial Property Rights)] 多能性幹細胞からの神経細胞の分化誘導方法 (2010)
  • Inventor(s): 影山龍一郎、小林妙子
  • Industrial Property Rights Holder: 国立大学法人京都大学
  • Industrial Property Number: 特許、PCT/JP2010/062014
  • Filing Date: 2010-07-15
• [Patent(Industrial Property Rights)] 多能性幹細胞からの神経細胞の分化誘導方法 (2009)
  • Inventor(s): 影山龍一郎、小林妙子
  • Industrial Property Rights Holder: 国立大学法人京都大学
  • Industrial Property Number: 特許、特願2009-168045
  • Filing Date: 2009-07-16