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1994 Fiscal Year Final Research Report Summary

発生・形態形成の個体レベルにおける分子生物学的研究

Research Project

Project/Area Number 06NP0901
Research Category

Grant-in-Aid for Creative Basic Research

Allocation TypeSingle-year Grants
Research InstitutionKyoto University

Principal Investigator

竹市 雅俊  京都大学, 理学部, 教授 (00025454)

Co-Investigator(Kenkyū-buntansha) 松居 靖久  東北大学, 加齢医学研究所, 助教授 (40241575)
山村 研一  熊本大学, 医学部, 教授 (90115197)
相沢 慎一  熊本大学, 医学部, 教授 (60073011)
黒岩 厚  名古屋大学, 理学部, 教授 (20134611)
安田 國雄  国立奈良先端科学技術大学院大学, バイオサイエンス研究科, 教授 (30025473)
Project Period (FY) 1993 – 1997
Keywords発生 / 遺伝子タ-デッティング / 形態形成 / 細胞分化 / 細胞認識 / 神経発生 / 遺伝子トラッピング / ES細胞
Research Abstract

1.脳におけるカドヘリンの発現パターンの詳細なマッピングを継続し、次の結果を得た。まず、初期胚の脳において複数のカドヘリンがニューロメアという構造単位を規定するように発現し、脳の分節化に重要な役割を果たしていることの証拠を得た。次に、カドヘリンがシナプスに存在する間接証拠を得た。これにより、カドヘリンが神経ネットワーク形成の鍵となる可能性が一層高まった。一方、ショウジョウバエの神経系において発現するカドヘリンを新たに同定し、その機能を分子遺伝学的に解明する手掛りを得た。
2.ニワトリαAクリスタリン遺伝子のエンハンサーに結合するL-mafの発現分布を調べた結果、将来水晶体に分化する外胚葉領域で発現が始まり、しかも体全体の中でこの領域だけが陽性であった。この発見は、L-mafが水晶体分化の中心的制御因子である可能性を示唆している。
3.始原生殖細胞由来EG細胞を生殖細胞欠失マウスに移植すると、生殖細胞特異的なマーカーにより認識される細胞が確認され、EG細胞から生殖細胞が誘導される可能性が示唆された。このシステムが確立すれば、生殖系の遺伝子操作が容易となりその意義は大きい。
4.RNA結合蛋白質musashi遺伝子がマウス中枢神経系の幹細胞特異的に発現していることを明らかにした。
5.ショウジョウバエの筋肉表面因子コネクチンをすべての筋肉で異所的に発現させることにより、神経-筋肉間の誘因的な認識分子として機能し得ることを明らかにした。また、F-スポンジンと相同性がある分子が一部の筋肉だけで発現されることを明らかにした。
6.消化管におけるHoxBクラスターの発現を調べ、特に肺において構造的区画及びBMP4,Wnt5aなどのシグナル因子の発現と相関する興味深い発現パターンを発見した。
7.Fak欠損マウスから細胞株を樹立し、細胞の移動能の低下、focal contactの欠失、microspikeの形成異常などを見い出した。また、Otx2欠損マウスを解析し、頭部の吻側、尾側の構造異常を認め、その頭部形成上の役割を証明した。
8.神経前駆細胞で発現するHES-1のノックアウトマウスを作製し解析したところ、無脳症になること、また、神経分化が早熟的に起きることがわかった。
9.初期発生の異常を引き起こすjmj遺伝子の構造を明らかにすると共に、新たに、胸腺、背部結合組織の異常を発見した。
10.マウス原腸形成に関与する遺伝子のクローニングのためにPCRディファレンシャルディスプレイ法を適用し、部域特異的に発現される遺伝子がクローニングできることが確認された。

  • Research Products

    (74 results)

All Other

All Publications (74 results)

  • [Publications] Oda,H.: "A Drosophila homolog of cadherin associated with Armadillo and essential for embryonic cell-cell adhesion." Develop.Biol.165. 716-726 (1994)

  • [Publications] Hatta,M.: "Complex cell type-specific transcriptional regulation by the promoter and an intron of the mouse P-cadherin gene." Develop.Growth & Differ.36. 509-519 (1994)

  • [Publications] Oyama,T.: "A truncated B-catenin disrupts the interaction between E-cadherin and α-catenin:A cause of loss of intercellular adhesiveness in human cancer cell lines." Cancer Res.54. 6282-6287 (1995)

  • [Publications] Shibamoto,S.: "Association of p120,a tyrosine kinase substrate,with E-cadherin/catenin complexes." J.Cell Biol.(in press). (1995)

  • [Publications] Overduin,M.: "Three-dimemsional solution structure and calcium interaction of the epithelial cadherin domain responsible for selective adhesion." Science. 267. 386-389 (1995)

  • [Publications] Nakagawa,S.: "Neural crest cell-cell adhesion controlled by sequential and subpopulation-specific exoression of novel cadherins." Development. (in press). (1995)

  • [Publications] Shibamoto,S.: "Tyrosine phosphorylation of β-catenin and plakoglobin enhanced by hepatocyte growth factor and epidermal growth factor in human carcinoma cells." Cell Adhesion & Commun.1. 295-305 (1994)

  • [Publications] Shiomi,K.: "Alternative cell fate choice induced by low-level expression of a regulator of protein phosphatase 2A in the Drosophila peripheral nervous system." Development. 120. 1591-1599 (1994)

  • [Publications] Uchiyama,N.: "Immunoelectron microscopic localization of E-cadherin in dorsal root ganglia,dorsal root and dorsal horn of postnatal mice." J.Neurocytol.23. 460-468 (1994)

  • [Publications] Shimamura,K.: "Wnt-1-dependent regulation of local E-cadherin and αN-catenin expression in the embryonic mouse brain." Development. 120. 2225-2234 (1994)

  • [Publications] Watabe,M.: "Induction of polarized cell-cell association and retardation of growth by activation of the E-cadherin-catenin adhesion system in a dispersedcarcinoma line." J.Cell Biol.127. 247-256 (1994)

  • [Publications] Nose,A.: "Ectopic expression of connection reveals a repulsive function during growth cone guidance and synapticformation." Neuron. 13. 525-539 (1994)

  • [Publications] Ishizaki,K.,: "IncreasedUV-induced SCEs in p53-.deficient mouse cells." Int.J.Cancer.58. 254-257 (1994)

  • [Publications] Tamemoto,H.,: "Targeted disruption of the insulin receptor substrate-1 gene results in insulin resistance and growth retardation." Nature. 372. 182-186 (1994)

  • [Publications] Nada,S.,: "Identification of majortyrosine-phosphorylatedproteins in Csk-deficient cells." Oncogene. 9. 3571-3578 (1994)

  • [Publications] Tojo,H.,: "Targeted Disruption of the neurotrophin-3 gene with lac Z induces loss of trk C-positive neurons in sensory ganglia but not in spinal cords" Brain Research.669. 163-175 (1994)

  • [Publications] Sakimura,K.,: "Reduced hippocampalLTP and spatiallearning inmice lacking NMDA receptor el subunit." Nature. (in press). (1994)

  • [Publications] Yoshida,M.,: "A new strategy of gene-trapping in ES cells using 3'RACE." Transgenic Research. (in press). (1994)

  • [Publications] Umemori,H.,: "Initial events of myelination involve Fyn tyrosine kinase signalling." Nature. 367. 572-576 (1994)

  • [Publications] Kubo,S.,: "A novel form of self tolerance dictated in the thymus of transgenic mice with autoreactive TCR a and b chain genes." Internatl.Immunol.6. 593-602 (1994)

  • [Publications] Hashimoto,N.,: "Parthenogenetic activation of oocytes,but normal spermatogenesis and somatic cell growth,by c-mos-deficiency in mice." Nature. 370. 68-71 (1994)

  • [Publications] Yagi,T.,: "Fyn expression during neurogenesis in mouse embryos." Oncogene. 9. 2433-2440 (1994)

  • [Publications] Tanaka,N.,: "Cellular commitment to oncogene-induced transformation or apoptosisis dependent on the transcription factor IRF-1." Cell. 77. 829-839 (1994)

  • [Publications] Kohmura,N.,: "A novel non-receptor tyrosine kinase,srm;cloning and targeted disruption." Mol.Cell.Biol.14. 6915-6925 (1994)

  • [Publications] Ilic,D.,: "Focal adhesion kinase is not essential for in vitro and in vivo differentiation of ES cells." Biochem.Biophys.Res.Commun. (in press). (1994)

  • [Publications] Hu,L.,: "P53 controls proliferation of early B lineage cells by a p21(WAF1/CIP1)-independent pathway." Biochem.Biophys.Res.Commun. 372. 182-186 (1994)

  • [Publications] Aizawa,S.,et al.: "Non-receptor tyrosine kinases in mammalian neurogenesis" Proceedings of the 24th International Symposium of the Princess Takamatsu Cancer Research Fund. 323-337 (1994)

  • [Publications] R.Sekido,: "δ-Crystallin enhancer binding protein δEF1 is a repressor of E2-box-mediated gene activation." Molecular and Cellular Biology. 14. 5692-5700 (1994)

  • [Publications] Y.Takahashi,: "Lens-specific activity of the chicken δ1-crystallin enhancer in the mouse." International Journal of Developmental Biology. 38. 365-368 (1994)

  • [Publications] S.Kamada,: "bcl-2 deficiency in mice leads to pleiotropic abnormalities:polycystic kidney etc." Cancer Research. 55. 354-359 (1995)

  • [Publications] Marshall,H.: "A conserved retinoic acid response element required for early expression of the homeobox gene Hoxb-1." Nature.370. 567-571 (1994)

  • [Publications] Studer,M.: "Role of a conserved retinoic acid response element in rhombomere-restriction of Hoxb-1." Science. 265. 1728-1731 (1994)

  • [Publications] Yokouchi,Y.: "Coordinated expression of Abd-B subfamily genes of the HoxA cluster in the developing digestive tract of chick embryo." Developmental Biology. 168(in press). (1995)

  • [Publications] Coffey,R.J.,: "Acceleration of mammary neoplasia in transforming growth factor α transgenic mice by 7,1-dimethylbenzanthracene." Cancer Research. 54. 1678-1683 (1994)

  • [Publications] Terajima,M.,: "Structural organization of the mouse glycophorin A gene." J.Biochem.116. 1105-1110 (1994)

  • [Publications] Kato,S.,: "Molecular cloning and expression of mouse Mg^<2+>・dependent protein phosphatase β-4(type2Cβ-4)." Arch.Biochem.Biophys.(in press). (1995)

  • [Publications] Matsubara,N.,: "Murine polo like kinase 1 gene is expressed in mciotic testicular germ cells and oocytes." Mol.Reprod.Dev.(in press). (1995)

  • [Publications] Nishiyori,A.,: "Determination of tissue specificity of the enhancer by combinatorial operation of tissue-enriched transcription factors." J.Biol.Chem.269. 1323-1331 (1994)

  • [Publications] Toyonaga,T.,: "Chronic active hepatltis in transgenic mice expressing interferon-γ in the liver." Proc.Natl.Acad.Sci.USA.91. 614-618 (1994)

  • [Publications] Kaname,T.,: "The upstream sequence of a new growth/differentiation factor,midkine(MK),mediates developmentally regulated lacZ gene expression in transgenic mice." Devlop.Growth Diifer.36. 231-238 (1994)

  • [Publications] Yamashita,S.,: "Group II phospholipase A2 in invasive gastric cancer cell line is induced by interleukin 6." Biochem.Biophys.Res.Com.198. 878-884 (1994)

  • [Publications] Nishiyama,Y.,: "Expression of the gene encoding the tyrosine kinase-deflcient human insulin receptor in transgenic mcie." 141. 187-192 (1994)

  • [Publications] Imamura,F.,: "The murine interleukin-5 receptor a-subunit gene:characterization of the gene Structure and chrimosome mapping." DNA Cell Biol.13. 283-292 (1994)

  • [Publications] Araki,S.,Yi: "Systemic amyloidosis in transgenic mice carrying the human mutant transthyretin(Me130)gene." Mol.Neurobiol.8. 15-23 (1994)

  • [Publications] Tashiro,F.,: "Resistance to cyclophosphamide-induced diabetes in transgenic NOD mice expressing l-A^k." Autolmmunity. 17. 181-188 (1994)

  • [Publications] Mantani,A.,: "A novel isoform of the neurofibromatosis type-1 mRNA and a switch of isoforms during murine cell differentiation and proliferation." Gene. 148. 245-251 (1994)

  • [Publications] Kimura,S.,: "Improvement of germ line transmission by targeting β-galactosidase to nuclei in transgenic mice." Devel.Growh Different.36. 521-527 (1994)

  • [Publications] 能瀬聡直: "Ectopic expression of Connectin reveals a repulsive function during growth cone guidance and synapse formation." Neuron. 13. 535-539 (1994)

  • [Publications] Nakamura,M.,: "MUSASHI,a neuronal protein required for Drosophlla adult external sensory organ development." Neuron. 13. 67-81 (1994)

  • [Publications] Kagawa,T.,: "Glial cell degeneration and hypomyelination caused by overexpression of the myelin proteollpid protein gene:implication for roles of the gene in differentiation and survival." Neuron. 13. 427-442 (1994)

  • [Publications] Xiong.W.C.,: "repo encodes a glial-specific homeodomain protein required in the Drosophila nervous system." Genes and Development. 8. 981-994 (1994)

  • [Publications] Okano,H.: "Cloning of a Drosophila melanogaster homologue of the mouse type-1BMP-2/-4 receptor:a potentlal decapentaplegic receptor." Gene. 148. 203-209 (1994)

  • [Publications] Sawamoto,K.,: "The function of argos in regulating cell fate decisions during the Drosophila eye and wing vein development." Developmental Blology. 164. 267-276 (1994)

  • [Publications] 安田國雄: "Functional conservation of the βB1-crystallin promoter between mouse and chicken." Develop.Biol.(in press). (1995)

  • [Publications] Makoto Ishihashi: "Persistent expression of helix-loop-helix factor HES-1 prevents mammalian neural differentiation in the central nervous system." EMBO Journal. 13. 1799-1805 (1994)

  • [Publications] Koichi Takebayashi,: "Structure,chromosomal locus,and promoter analysis of the gene encoding the mouse helix-loop-helix factorHES-1:negative autoregulation through the multiple N box elements." The Journal of Biological Chemistry. 269. 5150-5156 (1994)

  • [Publications] Teiji Sakagami,: "Structure and chromosomal locus of the mouse gene encoding a cerebellar Purkinje cell-specific helix-loop-helix factor HES-3." Biochemical and Biophysical Research Communications. 203. 594-601 (1994)

  • [Publications] Koichi Takebayashi,: "Structure and promoter analysis of the gene encoding the mouse helix-loop-helix factor HES-5:identification of the neural precursor cell-specific promoter element." The Journal of Biological Chemistry. 270. 1342-1349 (1995)

  • [Publications] Chihiro Akazawa,: "A mammalian helix-loop-helix factor structurally related to the product of Drosophila proneural gene atonal is a positive transcriptional regulator expressed in the developing nervous system." The Journal of Biological Chemistry. (in press). (1995)

  • [Publications] Chikara Shimizu,: "MATH-2,a mammalian helix-loop-helix factor structurally related to the product of Drosophila proneural gene atonal,is specifically expressed in the nervous system." European Journal of Biochemistry. (in press). (1995)

  • [Publications] Takahashi,M.,: "Molecular heterogeneity among primary motoneurons and within myotomes revealed by the differential mRNA expression of novel Islet-1 homologs in embryonic zebrafish." (submitted to Dev.Biol.).

  • [Publications] Inoue,A.,: "Developmental regulation of Isl-1 mRNA expression during neuronal differentation in embryonic zebrafish." Devel.Dynamics,. 197. 1-11 (1994)

  • [Publications] 岡本仁: "脳の形成はいかに遺伝子によって決定され、制御されているか(特集 神経科学の謎)" 生体の科学. 46. 2-7 (1995)

  • [Publications] 岡本仁: "ゼブラフィッシュ神経細胞の運命決定," プレインメヂカル,. 6. 135-142 (1994)

  • [Publications] 岡本仁: "ゼブラフィッシュの脊髄と運動神経細胞の分化〜転写因子と組織間相互作用の役割〜" 生体の科学. 45. 182-188 (1994)

  • [Publications] 竹内隆: "IRESを用いたマウス遺伝子トラップ法による神経管形成機構の解析" 組織培養. 21. 55-59 (1995)

  • [Publications] J.Cooke: "Experimental control of axial pattern in the chick blastoderm by localexpression of Wnt and activin:The role of HNK-1 positive cells." Developmental Biology. 164. 513-527 (1994)

  • [Publications] Shinji Takada: "Wnt-3a regulates somite andtailbud formation in the mouse embryo." Genes & Development. 8. 174-189 (1994)

  • [Publications] 相沢慎一: "バイオマニュアルシリーズ8 羊土社" ジーンターゲテイング:ES細胞を用いた変異マウスの作製, 174 (1994)

  • [Publications] 松居靖久: "最新・細胞内シグナル伝達ライブラリー(山本雅編)" 羊土社(印刷中), (1995)

  • [Publications] 松居靖久: "生殖細胞-基礎から最前線まで(岡田益吉・長濱嘉孝編)" 共立出版(印刷中), (1995)

  • [Publications] Okano,H.,: "Drosophila visual system as a model to study neurobiology in gencral:identification of genes regulating cell fate decision in ncural development.Basic Neuroscience in Invertebrate." Business Center for Academic Societies Japan,Ed II.Koike.(印刷中), (1995)

  • [Publications] Mikoshiba,K.,: "Molecular genetic analyses of the myelin deficiency and cerebellar ataxia in“Progress in Brain Research"" Elsevier(印刷中), (1995)

  • [Publications] 岡野栄之: "“モデル生物系を用いた中枢神経系の発生と分化の解析"脳機能の解明に向けて" 赤池紀扶ら編、創風社(印刷中), (1995)

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Published: 1996-04-15   Modified: 2016-04-21  

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