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Neuronal migration : its mechanism in normal development and pathologic changes in cerebral dysgenesis.

Research Project

Project/Area Number 10670753
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionJichi Medical School

Principal Investigator

MIZUGUCHI Masashi  Jichi Medical School, Department of Pediatrics, Associate Professor, 医学部, 助教授 (20209753)

Co-Investigator(Kenkyū-buntansha) TAKASHIMA Sachio  National Institute of Neuroscience, NCNP, Director General, 神経研究所, 所長(研究職) (70038743)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsLissencephaly / Subcortical laminar heterotopia / Fukuyama type congenital muscular dystrophy / Tuberous sclerosis / doublecortin / DCAMKL1 / hamartin / fukutin / LIS1 / Ekerラット / Zellweger症候群 / tuberin / telencephalin / 全前脳症
Research Abstract

1) Doublecortin is a product of the DCX gene responsible for X-linked lissencephaly and subcortical laminar heterotopia syndrome. DCAMKL 1 (or KIAA0369) is a calcium calmodulin-dependent kinase with high homology to doublecortin. We produced specific antibodies against these proteins, and studied their expression immunochemically and immunohistochemically. The results indicated specific expression of these proteins in the normally developing nervous system during the fetal period. Intense immunoreactivity was localilzed in migrating neurons. In migration disorders, doublecortin expression was downregulated in brains with Zellweger syndrome and in subcortical laminar heterotopia, whereas in those with tuberous sclerosis some abnormal giant cells showed its overdue expression.
2) Fukuyama type congenital muscular dystrophy (FCMD) is caused by a mutaion in the fukutin gene. We produced antibodies against fukutin protein, and studied its expression immunochemically and immunohisto-chemically. In brains of normal fetuses, high expression was noted in the granular layer at the cerebral surface, whereas fukutin was decreased in those of FCMD fetuses.
3) Tuberous sclerosis (TS) is caused by a mutation in either of the two tumor suppressor genes, TSC1 and TSC2, which encode hamartin and tuberin, respectively. In this study, we produced antibodies against hamartin, and studied its expression immunochemically and immunohisto- chemically. In the brain, kidney and heart of control patients, hamartin and tuberin co-localized. They showed simlutaneous loss in TS brain lesions, as well as in TS-associated renal and cardiac hamartomas. The brains of Eker rats, an animal model of TSC2, were studied pathologically. Two novel brain lesions, cortical tuber and anaplastic ganglioglioma, were found.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Mizuguchi,M., et al.: "High expression of doublecortin and KIAA0369 protein in fetal brain suggests their specific role in neuronal migration."American Journal of Pathology. 155. 1713-1721 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mizuguchi,M., et al.: "Novel cerebral lesions in the Eker rat model of tuberous sclerosis : cortical tuber and anaplastic gangliogioma."Journal of Neuropathology and Experimental Neurology. 59. 188-196 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mizuguchi,M., et al.: "Simultaneous loss of hamartin and tuberin from the cerebrum, kidney and heart with tuberous sclerosis."Acta Neuropathologica. 99. 503-510 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Qin,J., et al.: "Immunohistochemical expression of doublecortin in the human cerebrum : comparison of normal development and neuronal migration disorders."Brain Research. 863. 225-232 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Saito,Y., et al.: "Fukutin protein is expressed in neurons of the normal developing human brain but is reduced in Fukuyama-type congenital muscular dystrophy brain."Annals of Neurology. 47. 756-764 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Qin,J., et al.: "A novel migration-related gene product, doublecortin, in neuronal migration disorder of fetuses and infants with Zellweger syndrome."Acta Neuropathologica. 100. 168-173 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mizuguchi,M., et al.Niimura,M., et al(eds).: "Gann monograph on cancer research, vol.46, Phacomatosis in Japan"Japan Scientific Society Press. 229 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 水口雅: "領域別症候群シリーズ28・神経症候群III"日本臨牀社. 780 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mizuguchi, M., et al.: "High expression of doublecortin and KIAA0369 protein in fetal brain suggests their specific role in neuronal migration."American Journal of Pathology. 155(5). 1713-1721 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mizuguchi, M., et al.: "Novel cerebral lesions in the Eker rat model of tuberous sclerosis : cortical tuber and anaplastic gangliogioma."Journal of Neuropathology and Experimental Neurology. 59(3). 188-196 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mizuguchi, M., et al.: "Simultaneous loss of hamartin and tuberin from the cerebrum, kidney and heart with tuberous sclerosis."Acta Neuropathologica. 99(5). 503-510 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Qin, J., et al.: "Immunohistochemical expression of doublecortin in the human cerebrum : comparison of normal development and neuronal migration disorders."Brain Research. 863(1/2). 225-232 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Saito, Y., et al.: "Fukutin protein is expressed in neurons of the normal developing human brain but is reduced in Fukuyama-type congenital muscular dystrophy brain."Annals of Neurology. 47(6). 756-64 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Qin, J., et al.: "A novel migration-related gene product, doublecortin, in neuronal migration disorder of fetuses and infants with Zellweger syndrome."Acta Neuropathologica. 100(2). 168-173 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mizuguchi, M., et al.: "Neurological aspects of tuberous sclerosis."Niimura, M., Otsuka, F., Hino, O.(eds) Gann monograph on cancer research, vol. 46 Phacomatosis in Japan, Japan Scientific Society Press. 61-71 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mizuguchi,M., et al.: "Novel cerebral lesions in the Eker rat model of tuberous sclerosis : cortical tuber and anaplastic gangliogioma."Journal of Neuropathology and Experimental Neurology. 59(3). 188-196 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mizuguchi,M., et al.: "Simultaneous loss of hamartin and tuberin from the cerebrum, kidney and heart with tuberous sclerosis."Acta Neuropathologica. 99(5). 503-510 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Qin,J., et al.: "Immunohistochemical expression of doublecortin in the human cerebrum : comparison of normal development and neuronal migration disorders."Brain Research. 863(1/2). 225-232 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Saito,Y., et al.: "Fukutin protein is expressed in neurons of the normal developing human brain but is reduced in Fukuyama-type congenital muscular dystrophy brain."Annals of Neurology. 47(6). 756-764 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamanouchi,H., et al.: "Enhanced GAP-43 gene expression in cortical dysplasia."Neuroreport. 11(9). 1815-1819 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Qin,J., et al.: "A novel migration-related gene product, doublecortin, in neuronal migration disorder of fetuses and infants with Zellweger syndrome."Acta Neuropathologica. 100(2). 168-173 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mizuguchi,M.,et al.: "High expression of doublecortin and KIAA0369 protein in fetal brain suggests their specific role in neuronal migration"American Journal of Pathology. 155(5). 1713-1721 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Arii,N.,et al.: "Development of telencephalin in the human cerebrum"Microscopy Research and Technique. 16(1). 18-23 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Zhang,H.,et al.: "Mutational analysis of TSC1 and TSC2 genes in Japanese patients with tuberous sclerosis complex"Journal of Human Genetics. 44(2). 391-396 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Mizuguchi,M.,et al.: "Simultaneous loss of hamartin and tuberin from the cerebrum,kidney and heart with tuberous sclerosis"Acta Neuropathol. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Mizuguchi,M.,et al.: "Novel cerebral lesions in the Eker rat model of tuberous sclerosis : cortical tuber and anaplastic gangliogioma"Journal of Neuropathology and Experimental Neurology. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kato M,et al.: "Loss of neurofibromin in the leptomeningeal astroglial heterotopia of NF-1." Pediatric Neurology. 18(3). 227-230 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Obonai T,et al.: "Developmental and aging changes of Bak expression in the human brain." Brain Research. 783(1). 167-170 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Isumi H,et al.: "Expression of a 45k subunit platelet-activating factor acetylhydrolase in the developing mouse cerebellum." Anatomy and Embryology. 197(5). 415-419 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takashima S,et al.: "Neuronal migration disorder:Expression of gene products in the neocortex." Neuropathology. 18(4). 427-432 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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