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Abnormal Craniofacial Morphogenesis of the Small Eye Rat

Research Project

Project/Area Number 08457475
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Morphological basic dentistry
Research InstitutionNational Center of Neurologu & Psychiatry (1997-1998)
Tokyo Medical and Dental University (1996)

Principal Investigator

OSUMI Noriko  National Center of Neurology & Psychiatry, National Institute of Neuroscience, Head Investigator, 神経研究所・疾病研究第七部, 室長 (00220343)

Co-Investigator(Kenkyū-buntansha) ETO Kazuhiro  Tokyo Medical & Dental University, Department of Developmental Biology, Professo, 歯学部, 教授 (30014161)
青木 香織  東京医科歯科大学, 歯学研究科, 助手 (00276213)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1996: ¥5,000,000 (Direct Cost: ¥5,000,000)
KeywordsPax-6 gene / Mutant rat / Midbrain / Crest cells / Cell migration / Craniofacial abnormality / Lewis X / Fucosyltransferase / LewisX糖鎖 / HNK-1 epitope / 内田ラット / 哺乳類全胚培養 / 頭部神経堤細胞 / 運動神経 / Islet-2遺伝子 / 体性運動性神経
Research Abstract

Craniofacial Morphogenesis of vertebrates includes complex processes such as formation of the neural tube, migration and differentiation of neural crest cells, and development of sensory organs and nervous systems. Any failures in these developmental processes result in various congenital deseases, e.g., excencephaly, cleft lip and palate, micrognathia ; malformed teeth etc. In the present research project, we used a mutant rat strain called Small eye rat (rSey2) as a good model for analyzing craniofacial morpho-genesis in mammals. The Small eye rat has a mutation in Pax6 gene encoding a transcription factor. Pax6 is originally cloned by homology with Drosophila gene called paired. Homozygous new born has no eyes and no nose and exhibit severe craniofacial malformations. We identified that impaired migration of midbrain crest cells into the frontonasal mass leads to dysplasia of nasal cartilage and related facial bones. Pax6 gene expression is absent from the crest cells but positive i … More n the frontonasal epithelium, i.e., the pathway for midbrain crest cells. Normal crest cells isolated fromthe wild-type midbrain failed to migrate into the frontonasal mass in the host mutant embryos. Therefore, Pax6 is suggested to influence the midbrain crest cell migration toward the frontonasal mass in a cell non-autonomous mechanism. We also found that LewisX is distributed in the frontonasal epithelium of the wild type embryos, while it is absent from the mutant epithelium. Instead, the frontonasal epithelium of the mutant expressed HNK-1 epitope, which shares a common precursor with LewisX.Biochemical analyses showed that enzyme activity of fucosyltransferase, which is involved in synthesis of Lewis X, was drastically lower in the homozygotes. Among various genes encoding fucosyltransferases, we identified that expression of FucT IX, a novel fucosyltransferase gene, is specifically lost in the mutant. From these results, Pax6 is suggested to be important in craniofacial morphogenesis through controling migration of midbrain crest cells toward the frontnasal mass. Less

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (39 results)

All Other

All Publications (39 results)

  • [Publications] Imai, H., Osumi, N., and Eto, K.: "Contribution of foregut endoderm to tooth initiation of mandibular incisor in rat embryos." Eur.J.Oral Sci.106. 19-23 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kurisaki T, Masuda A, Osumi N, et al.: "Spatially-and temporally-restricted expression of meltrin alpha(ADAM12)and beta(ADAM19)in mouse embryo." Mech Dev. 73. 211-215 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 大隅典子: "メオボックス遺伝子による脳のパターニング" 遺伝子医学. 16. 524-528 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Torii, M., Matsuzaki, F., Osumi, N, et al.: "Transcription factors Mash-1 and Prox-1 delineate early steps in differentiation of neural stem cells in the developing central nervous system." Development. 126. 443-456 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawano, H., Fukuda, T., Kubo, K., Horie, M., Takeuchi, K., Osumi, N., et al.: "Pax6 is required for the thalamocortical pathway formation in fetal rats." J.Comp.Neurol.in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 井上高良、大隅典子: "無敵のバイオテクニカルシリーズ特別編「脳・神経研究の進め方」第3章5)中枢神経系の形態形成〜哺乳類全胚培養系を用いた研究例" 羊土社 真鍋俊也、森 寿、片山正寛編集, 109-113 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Osumi, N.and Nakafuku, M.: "Pax-6 is involved in specification of ventral cell types in the hindbrain. In Neural Development : Keio Univ.Symposia for Life Science and Medicine : Vol.2" Springer-Verlag Tokyo, K.Uyemura, K.Kawamura, T.Yazaki(Eds), 117-124 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Osumi-Yamashita, N., Ninomiya, Y., Doi, H.and Eto, K.: "Rhombomere formation and hindbrain crest cell migration from prorhombomeric origins in mouse embryos." Develop.Growth Differ.38. 107-118 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Imai, H., Osumi-Yamashita, N., Ninomiya, Y., and Eto, K.: "Contribution of early-emigrating midbrain crest cells to the dental mesenchyme of the mandibular molar tooth in rat embryos." Develop.Biol.176. 151-165 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Osumi-Yamashita, N., Kuratani, S., Ninomiya, Y., Aoki, K., Iseki, S., Chareonvit, S., Doi, H., Fujiwara, M., Watanabe, T.and Eto, K.: "Cranial anomaly of homozygous rSey rat is associated with a defect in the migration pathway of midbrain crest cells." Devel.Growth & Differ.39. 53-67 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chareonvit, S., Osumi-Yamashita, N., Ikeda, M., and Eto, K.: "Murine forebrain and midbrain crest cells generate different characteristic derivatives in vitro." Develop.Growth Differ.39. 493-503 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Osumi, N., Hirota, A., Ohuchi, H., Nakafuku, M., Iimura, T., Kuratani, S., Fujiwara, M., Noji, S.and Eto, K.: "Pax-6 is involved in specification of the hindbrain motor neuron subtype." Development. 124. 2961-297 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Imai, H., Osumi, N., and Eto, K.: "Contribution of foregut endoderm to tooth initiation of mandibular incisor in rat embryos." Eur.J.Oral Sci.106(Supple 1). 19-23 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kurisaki T, Masuda A, Osumi N,Nabeshima Y,and Fujisawa-Sehara A.: "Spatially-and temporally-restricted expression of meltrin alpha (ADAM12) and beta (ADAM19) in mouse embryo." Mech Dey. 73. 211-215 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Torii, M., Matsuzaki, F., Osumi, N., Kaibuchi, K., Nakamura, S., Casarosa, S., Guillemot, F., and Nakafuku, M.: "Transcription factors Mash-1 and Prox-1 delineate early steps in differentiation of neural stem cells in the developing central nervous system." Development. 126. 443-456 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawano, H., Fukuda, T., Kubo, K., Horie, M., Takeuchi, K., Osumi, N., Eto, K., and Kawamura, K.: "Pax6 is required for the thalamortical pathway formation in fetal rats." J.Comp.Neurol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Osumi-Yamashita, N.: "Retinoic acid and mammalian craniofacial morphogenesis." J.Biosci.21. 313-327 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Osumi-Yamashita N., Ninomiya, Y.and Eto K.: "Craniofacial embryology in vitro." Int.J.Devel.Biol.41. 187-197 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Imai,H.,Osumi,N.,and Eto,K.: "Contribution of foregut endoderm to tooth initiation of mandibular incisor in rat embryos." Eur.J.Oral Sci.106. 19-23 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kurisaki T,Masuda A,Osumi N,et al.: "Spatially-and temporally-restricted expression of meltrin alpha(ADAM12)and beta(ADAM19)in mouse embryo." Mech Dev. 73. 211-215 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 大隅典子: "ホメオボックス遺伝子による脳のパターニング" 遺伝子医学. 16. 524-528 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Torii,M.,Matsuzaki,F.,Osumi,N,et al.: "Transcription factors Mash-1 and Prox-1 delineate early steps in differentiation of neural stem cells in the developing central nervous system." Development. 126. 443-456 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kawano,H.,Fukuda,T.,Kubo,K.,Horie,M.,Takeuchi,K.,Osumi,N.,et al.: "Pax6 is required for the thalamocortical pathway formation in fetal rats." J.Comp.Neurol.(in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] 井上高良、大隅典子: "無敵のバイオテクニカルシリーズ特別編「脳・神経研究の進め方」第3章 5)中枢神経系の形態形成〜哺乳類全胚培養系を用いた研究例" 羊土社 真鍋俊也、森 寿、片山正寛編集, 109-113 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Osumi,N.and Nakafuku,M.: "Pax-6 is involved in specification of ventral cell types in the hindbrain.In Neural Development:Keio Univ.Symposia for Life Science and Medicine:Vol.2" Springer-Verlag Tokyo,K.Uyemura,K.Kawamura,T.Yazaki(Eds), 117-124 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Osumi-Yamashita N.et al.: "Cranial anomaly of homozygous rSey rat is associated with a defect in the migration pathway of midbrain crest cells." Devel.Growth&Differ.39. 53-67 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Chareonvit,S.et al: "Murine forebrain and midbrain crest cells generate different characteristic derivatives in vitro." Develop.Growth Differ.39. 493-503 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Osumi,N.et al.: "Pax-6 is involved in specification of the hindbrain motor neuron subtype." Development. 124. 2961-297 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Osumi-Yamashita N.et al.: "Craniofacial embryology in vitro." Int.J.Devel.Biol.41. 187-194 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 大隅典子: "レチノイン酸と哺乳類の胚発生-奇形学から発生生物学へ" 細胞工学. 16(5). 696-705 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 大隅典子: "神経堤細胞と頭部形成" 細胞. 29. 415-421 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 倉谷 滋、大隅典子: "神経堤細胞‐脊椎動物のボディプランを支えるもの" UPバイオロジー、東大出版会, 130 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Imai,H.,Osumi-Yamashita,N.,Ninomiya,Y.,and Eto,K.: "Contribution of early-emigrating midbrain crest cells to the dental mesenchyme of the mandibular molar tooth in rat embryos." Developmental Biology. 176. 151-165 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Osumi-Yamashita,N: "Retinoic acid and mammalian craniofacial morphogenesis." J.Biosci.21. 313-327 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 倉谷滋、大隅-山下典子: "篩骨とは何か.II.発生学的考察" The Bone. 10. 171-181 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 大隅-山下典子: "感覚器形成の分子機構" 実験医学増刊. 14. 186-192 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Osumi-Yamashita N.and Eto K: "Craniofacial embryology in vitro." Int.J.Devel.Biol.(in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Osumi-Yamashita,N et al.: "Cranial anomaly of homozygous rSey rat is associated with a defect in the migration pathway of midbrain crest cells." Devel.Growth & Differ.(in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] 大隅-山下典子、二宮洋一郎、江藤一洋: "「神経生物学研究に必要な胚と個体の遺伝子操作法」ニューロサイエンスラボマニュアル 3 神経発生研究における哺乳類全胚培養法." シュプリンガー・フェアラーク東京 近藤寿人 編集 (in press), (151-165)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2018-02-02  

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