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Molecular Mechanisms for Synapse Formation and Inter-Neuronal Connection

Research Project

Project/Area Number 10102006
Research Category

Grant-in-Aid for Specially Promoted Research

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionRIKEN (2002)
Kyoto University (1998-2001)

Principal Investigator

TAKEICHI Masatoshi  RIKEN Center for Developmental Biology, Group Director, 高次構造形成研究グループ, グループディレクター (00025454)

Co-Investigator(Kenkyū-buntansha) UEMURA Tadashi  Kyoto University, Faculty of Science, Associate Professor, 理学研究科, 助手 (80213396)
CHISAKA Osamu  Kyoto University, Faculty of Science, Associate Professor, 理学研究科, 助教授 (80188474)
Project Period (FY) 1998 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥361,200,000 (Direct Cost: ¥321,000,000、Indirect Cost: ¥40,200,000)
Fiscal Year 2002: ¥87,100,000 (Direct Cost: ¥67,000,000、Indirect Cost: ¥20,100,000)
Fiscal Year 2001: ¥87,100,000 (Direct Cost: ¥67,000,000、Indirect Cost: ¥20,100,000)
Fiscal Year 2000: ¥47,000,000 (Direct Cost: ¥47,000,000)
Fiscal Year 1999: ¥60,000,000 (Direct Cost: ¥60,000,000)
Fiscal Year 1998: ¥80,000,000 (Direct Cost: ¥80,000,000)
Keywordscadherin / catenin / synapse / neuron / hippocampus / cell adhesion / cerebellum / Purkinje cell / 神経回路 / プルチンエ細胞 / シナプシン / PSD-95 / 網膜 / 脳 / LTP / p120
Research Abstract

1. We have shown that under the suppression of cadherin function, dendritic spines abnormally elongate, axon-spine contacts are destabilized, and presynaptic vesicle accumulation and postsynaptic density protein organization are impaired. These findings provide the first compelling evidence for the important role of cadherin in synapse formation and maintenance
2. We analyzed hippocampal neurons collected from αN-catenin mutant mice, and found that their dendritic spines abnormally elongated, genetically confirming the above in vitro results. We also found that, in the cerebellum of αN-catenin knockout mice, Purkinje cell migration is partly blocked, suggesting that this catenin is also important for the migration of particular subsets of neuronal precursors.
3. Cadherin-11 knockout mice showed aberrant emotional behavior, such as reduced anxiety, suggesting that this cadherin is involved in the regulation of physiological brain functions. Cadherin-8 knockout mice show another behavioral phenotypes, which are under detailed investigation.
4. We found that p120-catenin has the activity to bind cytoplasmic microtubules, suggesting that p120-catenin functions as a linker between microtubules and cell-cell junctions, controlling microtubule networks. This is the first demonstration for the interactions of the cadherin and microtubule systems.
5. We discovered that the seven-passed transmembrane cadherin Flamingo plays a role in the regulation of planer cellular polarity.
6. We identified a unique cadherin, present in both vertebrates and invertebrates, and in the former, it is specifically expressed in the outerplexiform layer of retina.

Report

(6 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (51 results)

All Other

All Publications (51 results)

  • [Publications] Inoue, T., Tanaka, T., Suzuki, S.C., Takeichi, M.: "Cadherin-6 in the developing mouse brain : expression along restricted connection systems and synaptic localization suggest a potential role in neuronal circuitry"Developmental Dynamics. 211. 338-351 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aono, S., Nakagawa, S., Reynolds, A.B., Takeichi, M.: "p120^<ctn> acts as an inhibitory regulator of cadherin function in colon carcinoma cells"J.Cell Biology. 145. 551-562 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Usui, T., Shima, Y., Shimada, Y., Hirano, S., Burgess, R.W., Schwarz, T.L., Takeichi, M., Uemura, T.: "Flamingo, a seven-pass transmembrane cadherin, regulates planar cell polarity under the control of Frizzled"Cell. 98. 585-595 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Honjo, Y., Nakagawa, S., Takeichi, M.: "Blockade of cadherin-6B activity perturbs the distribution of PSD-95 family proteins in retinal neurons"Genes to Cells. 5. 309-318 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Honjo, M., Tanihara, H., Suzuki, S., Tanaka, T., Honda, Y., Takeichi, M.: "Differential expression of cadherin adhesion receptors in neural retina of the postnatal mouse"Invest.Ophthalmol.Vis.Sci.. 41. 546-551 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Manabe, T., Togashi, H., Uchida, N., Suzuki, S.C., Hayakawa, Y, Yamamoto, M., Yoda, H., Miyakawa, T., Takeichi, M., Chisaka, O.: "Loss of cadherin-11 adhesion receptor enhances plastic changes in hippocampal synapses an modifies behavioral responses"Mol.Cell.Neuroscience. 15. 534-546 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimada, Y., Usui, T., Yanagawa, S., Takeichi, M., Uemura, T.: "Asymmetric colocalization of Flamingo, a seven-pass transmembrane cadherin, and Dishevelled in planar cell polarization"Current Biology. 11. 859-863 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Horikawa, K., Takeichi, M.: "Requirement of juxtamembrane domain of the cadherin cytoplasmic tail for morphogenetic cell rearrangement during myotome development"J.Cell Biology. 155. 1297-1306 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwai, Y., Hirota, Y., Ozaki, K., Okano, H., Takeichi, M., Uemura, T.: "DN-Cadherin is required for spatial arrangement of axon terminals and their targets, and ultrastructural organization of synapses in the Drosophila visual system"Mol.Cell.Neuroscience. 19. 375-378 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Togashi, H., Abe, K., Mizoguchi, A., Chisaka, O., Takeichi, M.: "Cadherin regulates dendritic spine morphogenesis"Neuron. 35. 77-89 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Inoue, T., Tanaka, T., Suzuki, S. C., and Takeichi, M.: "Cadherin-6 in the developing mouse brain : expression along restricted connection systems and synaptic localization suggest a potential role in neuronal circuitry"Developmental Dynamics. 211. 338-351 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aono, S., Nakagawa, S., Reynolds, A. B., and Takeichi, M.: "p120^<ctn> acts as an inhibitory regulator of cadherin function in colon carcinoma cells"J. Cell. Biology. 145. 551-562 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Usui, T., Shima, Y., Shimada, Y., Hirano, S., Burgess, R. W., Schwarz, T. L., Takeichi, M., and Uemura, T.: "Flamingo, a seven-pass transmembrane cadherin, regulates planar cell polarity under the control of Frizzled"Cell. 98. 585-595 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Honjo, Y., Nakagawa, S., and Takeichi, M.: "Blockade of cadherin-6B activity perturbs the distribution of PSD-95 family proteins in retinal neurons"Genes to Cells. 5. 309-318 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Honjo, M., Tanihara, H., Suzuki, S., Tanaka, T., Honda, Y, and Takeichi, M.: "Differential expression of cadherin adhesion receptors in neural retina of the postnatal mouse"Invest. Ophthalmol. Vis. Sci.. 41. 546-551 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Manabe, T., Togashi, H., Uchida, N., Suzuki, S. C., Hayakawa, Y., Yamamoto, M., Yoda, H., Miyakawa, T., Takeichi, M., and Chisaka, O.: "Loss of cadherin-11 adhesion receptor enhances plastic changes in hippocampal synapses an modifies behavioral responses"Mol. Cell. Neuroscience. 15. 534-546 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimada, Y., Usui, T., Yanagawa, S., Takeichi, M., and Uemura, T.: "Asymmetric colocalization of Flamingo, a seven-pass transmembrane cadherin, and Dishevelled in planar cell polarization"Current Biology. 11. 859-863 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Horikawa, K., and Takeichi, M.: "Requirement of juxtamembrane domain of the cadherin cytoplasmic tail for morphogenetic cell rearrangement during myotome development"J. Cell Biology. 155. 1297-1306 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwai, Y., Hirota, Y., Ozaki, K., Okano, H., Takeichi, M., and Uemura, T.: "DN-Cadherin is required for spatial arrangement of axon terminals and their targets, and ultrastructural organization of synapses in the Drosophila visual system"Mol. Cell. Neuroscience. 19. 375-378 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Togashi, H., Abe, K., Mizoguchi, A., Chisaka, O., and Takeichi, M.: "Cadherin regulates dendritic spine morphogenesis"Neuron. 35. 77-89 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwai, Y., Hirota, Y., Ozaki, K., Okano, H., Takeichi, M., Uemura, T.: "DN-Cadherin is required for spatial arrangement of axon terminals and their targets, and ultrastructural organization of synapses in the Drosophila visual system"Mol. Cell. Neuroscience. 19. 375-378 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Niwa, R., Nagata-Onishi, K., Takeichi, M., Mizuno, K., Uemura, T.: "Control of actin reorganization by Slingshot, a family of phosphatases that dephosphorylate ADF/cofilin"Cell. 108. 233-246 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shima, Y., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Chisaka, O., Takeichi, M., Uemura, T.: "Differential expression of the seven-pass trarsmembrane cadherin genes Celsr1-3 and distribution of the Celsr2 protein during mouse development"Developmental Dynamics. 223. 321-323 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Umemiya, T., Takasu, E., Takeichi, M., Aigaki, T., Nose, A.: "Forked end : a novel transmembrane protein involved in neuromuscular specificity in Drosophila identified by gain-of-function screening"J. Neuroscience. 51. 205-214 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Togashi, H., Abe, K., Mizoguchi, A., Chisaka, O., Takeichi, M.: "Cadherin regulates dendritic spine morphogenesis"Neuron. 35. 77-89 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kubo, F., Takaichi, M., Nakagwa, S.: "Wnt2b controls retinal cell differentiation at the ciliary marginal zone"Development. 130. 587-598 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Inoue, T., Takeichi, M.: "Role of cadherins in maintaining the compartment boundary between the cortex and striatum during development"Develop. Biol.. 128. 561-569 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kataoka, Y., Takeichi, M.: "Developmental roles and molecular characterization of a Drosophila homologue of Arabidopsis Argonaute1, the founder of a novel gene superfamily"Genes to Cells. 6. 313-325 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shimada, Y., Uemura, T.: "Asymmetric colocalization of Flamingo, a seven-pass transmembranecadherin, and Dishevelled in planar cell polarization"Current Biology. 11. 859-863 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Watari, N., Chisaka, O.: "Hoxa3 regulates integration of glossopharyngeal nerve precursor cells"Develop. Biol.. 240. 15-31 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Iwai, Y., Uemura, T.: "DN-Cadherin is required for spatial arrangement of axon terminals and their targets, and ultrastructual organization of synapses in the Drosophila visual system"Mol. Cell. Neuroscience. (in press). (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Horikawa, K., Takeichi, M.: "Requirement of juxtamembrane domain of the cadherin cytoplasmic tail for morphogenetic cell rearrangement during myotome development"J. Cell Biol.. 155. 1297-1306 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Niwa, R., Uemura, T.: "Control of actin reorganization by Slingshot, a family of phosphatases that dephosphorylate ADF/cofilin"Cell. 108. 233-246 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Umemiya, Y., Nose, A.: "Forked end : a novel transmembrane protein involved in neuromuscular neuromuscular specificity in Drosophila identified by gain-of-function screening"J. Neurobiol.. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Honjo,M.,and Takeichi,M.: "Differential expression of cadherin adhesion receptors in neural retina of the postnatal mouse."Invest.Ophthalmol.Vis.Sci.. 41. 546-551 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yagi,T.and Takeichi,M.: "Cadherin superfamily genes : functions, genomic organization, and neurologic diversity."Genes & Dev.. 14. 1169-1180 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Manabe,M.,and Takeichi,M.: "Loss of cadherin-11 adhesion receptor enhances plastic changes in hippocampal synapses and modifies behavioral responses."Mol.Cell.Neuroscience. 15. 534-546 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takeichi,M.,and Uemura,T.: "Patterning of cell assemblies regulated by adhesion receptors of the cadherin superfamily."Phil.Trans.R.Soc., Lond.B. 355. 885-890 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Inoue.T.,and Takeichi,M.: "Role of cadherins in maintaining the compartment boundary between the cortex and striatum during development."Development. 128. 561-569 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Wohrn, J-C. P. et al.: "Combinatorial expression of cadherins in the tectum and the sorting of neurites in the tectofugal pathways of the chicken embryo"Neuroscience. 90. 985-1000 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Aono, S. et al.: "p120cm acts as an inhibitory regulator of cadherin function in colon carcinoma cells"J. Cell Biology. 145. 551-562 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Horikawa, K. et al.: "Adhesive subdivisions intrinsic to the epithelial somites"Developmental Biolology. 215. 182-189 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Usui, T. et al.: "Flamingo, a seven-pass transmembrane cadherin, regulates planar cell polarity under the control of Frizzled"Cell. 98. 585-595 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Honjo, Y. et al.: "Blockade of Cadherin-6B Activity Perturbs the Distribution of PSD-95 Family Proteins in retinal Neurons"Genes to Cells. (印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Redies, C. et al.: "Morphological fate of diencephalic prosomeres and their subdivisions revealed by mapping cadherin expression"J. Comparative. Neurology. (印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Inoue,T.et al.: "Cadherin-6 in the developing mouse brain: Expression along restricted connection systems and synaptic localization suggest a potential role in neuronal circuitry." Develop.Dynamics. 211. 338-351 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Arndt,K.et al.: "Cadherin-defined segment and parasagittal cell ribbons in the developing chicken cerebellum." Mol.Cell.Neuroscience. 10. 211-228 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Wohrn,J-C.P.et al.: "Cadherin expression in the retina and retinofugal pathways of the chicken embryo." J.Comp.Neurology. 396. 20-38 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shishido,E.et al.: "Drosophila synapse formation: Regulation by transmembrane protein with Leu-rich repeats,Capricous." Science. 280. 2118-2121 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakagawa,S.et al: "Neural crest emigrafion from the neural tube depends on regulated cadherin expression." Development. 125. 2963-2971 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Watabe-Uchida,M.et al: "α-Catenin-vinculin interaction functions to organize the apical junctional complex in epithelial cells.." J.Cell Biol.142. 847-857 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2018-03-28  

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