1993 Fiscal Year Annual Research Report

発生・形態形式の個体レベルにおける分子生物学的研究

Research Project

Project/Area Number	05NP0901
Research Institution	Kyoto 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, 助手 (40241575) 山村研一熊本大学, 医学部, 教授 (90115197) 相沢慎一理化学研究所, 筑波ライフサイエンスセンター, 副主任研究員 (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, 教授 (30025473)
Keywords	発生 / 遺伝子ターゲッティング / 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	ニワトリ及びマウス初期胚において発現する新しいカドヘリンを複数同定し発現を調べた。そのうちあるものは、神経冠の一部の細胞だけが発現し、しかも、その細胞は特定の限られた組織に分化した。これは、神経冠細胞群が分化方向に応じて異なるカドヘリンを発現し、その行動制御に関わることを示唆している。また、他のカドヘリンは、神経管の融合部位のみ、あるいは特定の神経核のみで発現されるなど、形態形成上興味深い多くの発現パターンが明らかになった。一方、ショウジョウバエのカドヘリンを同定することに成功し、無脊椎動物にもカドヘリンが存在することを初めて示した。ニワトリalphaAクリスタリン遺伝子のエンハンサーalphaCE1領域に結合する因子のcDNAクローンを得た。この因子は、ショウジョウバエ転写因子Elflと相同性があった。またalphaCE2結合因子はc-mafであることが判明した。さらに、deltaクリスタリン発現抑制因子deltaEF1がE2boxに対して抑制因子として働くこと、deltaEF2がSoxファミリーに属することが明らかになった。deltaEF2の強制発現はdeltaクリスタリンエンハンサーを活性化した。さらに、deltaEF1欠損マウスの作製に成功した。始原生殖細胞特異的なレセプター型キナーゼ遺伝子を4種類分離した。このうちGCK3はPolo様キナーゼで、精原細胞、精母細胞、卵母細胞で発現されていた。遺伝子トラップにより得られたAyul遺伝子は大脳皮質後頭葉や十二指腸神経節で発現され、その遺伝子座の近傍にlethal spottingという遺伝子変異が存在することが明らかになった。ショウジョウバエrepo遺伝子を解析し、グリア細胞特異的に発現され、神経遊走のguidance cueとしての役割を持つことを示唆した。また、ショウジョウバエ神経得意的RNA結合因子musashiのマウス相同遺伝子の単離に成功した。ショウジョウバエにおいて特定の筋肉のみで発現するコネクチンcDNAをTollのエンハンサーにつなぎ他の筋肉で異所的に発現させると、運動神経の遊走異常が起きることを発見した。この結果は、コネクチンが神経、筋肉認識因子として作用することを初めて示したものである。消化管の領域特異的な分化と、Hox遺伝子群の発現パターンの関係を調べた。その結果、Hoxa-4、Hoxa-5、Hoxa-6の前方発現境界は、それぞれ、前胃と食堂、前胃と左嚢、砂嚢と十二指腸の境界にあった。これは、消化管の領域特異的分化にHox遺伝子群が関与していることを示唆している。チロシンキナーゼsrm、Fakの欠損マウスを作製した。後者は体幹部に形成異常があったが頭部は正常であった。また、前年度作製したCsk欠損マウスの神経上皮は培養下では正常に増殖分化することを明らかにした。

Research Products
(37 results)

All Other

All Publications (37 results)

[Publications] Uemura,T.,Shiomi,K.,Takeichi,M.,その他: "Mutation of twins encoding a regulator of protein phosphatase 2A leads to pattern duplication in Drosophila imaginal discs." Genes and Development. 7. 429-440 (1993)
[Publications] Fujimori,T.,Takeichi,M.: "Disruption of epithelial cell-cell adhesion by exogenous expression of a mutated non-functional N-cadherin.21GC02:Molecular Biology of the cell" 4. 37-47 (1993)
[Publications] Oda,H.,Uemura,T.,Takeichi,M.,その他: "Identification of a Drosophila homologue of alpha-catenin and its association with the armadillo protein." Journal of Cell Biology. 121. 1133-1140 (1993)
[Publications] Redies,C.,Takeichi,M.: "Expression of N-cadherin mRNA during development of the mousebrain." Developmental Dynamics. 197. 26-39 (1993)
[Publications] Matsunami,H.,Miyatani,S.,Takeichi,M.,その他: "Cell binding specificity of mouse R-cadherin and chromosomal mapping of the gene." Journal of Cell Science. 106. 401-409 (1993)
[Publications] Watabe,M.,Matsumoto,K.,Takeichi,M.,その他: "Effect of hepatocyte growth factor on cadherin-mediated cell-cell adhesion." Cell Structure and Function. 181. 117-124 (1993)
[Publications] Uchida,N.,Shimamura,K.,Takeichi,M.,その他: "MousealphaN-catenin,two isoforms,specific expression in the nervous system and chromosomal localization of the gene." Developmental Biology. in press. (1994)
[Publications] Okada,T.S.,Yasuda,K.: "How are non-lenticular cells ready for transdifferentiation?" Developmental Dynamics. 196. 273-275 (1993)
[Publications] Kitamura,M.,Miyauchi,K.,Yasuda,K.: "Purification and immunological analyses of a nuclear factor,alphaCE1,that binds to a lens-specific enhacer of the chicken alphaA-crystallin gene." Nucleic Acids Research. accepted. (1994)
[Publications] Niwa,H.et al.: "Anefficient gene-trap method using poly A trap vectors and characterization of gene-trap events." J Biochem. 113. 343-349 (1993)
[Publications] Yamamura,K.et et al: "Transgenic mouse model for human genetic diseases" Mol.Reprod.Dev.36. 248-250 (1993)
[Publications] Pierce,D.F.et al: "Inhlbltlon of mammary duct development but not alveolar outgrowth during pregnancy In MMTV-TGFbeta1s223/225 transgenic mice." Gene&Development. 7. 2308-2317 (1993)
[Publications] Coffey,R.J.et al: "Acceleratlon of mammary neoplasia in virgrln mouse mammary tumor virus enhancer /promotor-transformng growth factor alphatransgenic mice by 7,12 dlmethylbenzanthracene." Caner Research. (1994)
[Publications] 松居靖久: "始原生殖細胞由来の細胞株の胚幹細胞としての性質" 日本疾患モデル学会記録. 9. 9-14 (1993)
[Publications] 松居靖久: "始原生殖細胞株の樹立とその性質" Tissue Culture Research Communications. 12. 273-278 (1993)
[Publications] Sawai,S.et al.: "Defects of embryonic organogenesis resulting from targeted distruption of the N-myc gene in the mouse." Development. 117. 1445-1455 (1993)
[Publications] Kamachi,Y.,Konodoh,H.: "Overlapping positive and negative elements determine lens specificity of the delta1-crystallin enhancer." Molecular and Celluar Biology. 13. 5206-5213 (1993)
[Publications] Funahashi,J.et el: "delta-Crystallin enhancer binding protein deltaEF1 is a zinc finger-homeodomain protein implicated in post gastrulation embryogenesis." Development. 119. 433-446 (1993)
[Publications] Tomotsune,D.et al.: "A mouse homologue of the Drosophila tumor-suppressor gene 1(2)gl controlled by Hox-C8 in vivo." Nature. 365. 69-72 (1993)
[Publications] Yosikawa,S.,Miyamoto,I.et al: "Isolation of a Drosophila Gene Encoding a Head-Specific Guanylyl cyclase." J.Neurochem. 60. 1570-153 (1993)
[Publications] Kume,S.,Muto,A.et al.: "The Xenopus IP3 Receptor;structure,function and localization in oocytes and eggs." Cell. 73. 555-570 (1993)
[Publications] Xing,W.C.,Okano,H.et al: "repo encodes a glial-specific homeodomain protein required in the Drosophila nervous system." Genes and Development in press.
[Publications] 岡野栄之、澤本和延ら: "神経細胞の分化と軸策走行を制御するEGFモチーフを持つ新しい分泌性因子・strawberry遺伝子産物。" 神経科学. 32. 162-163 (1993)
[Publications] Koyama,E.et al: "Cooperative actlvation of HoxD homeobox genes by factors from the polarizing region and apical ridge in chick limb morphogenesis." Develop Growth&Differ. 35. 189-198 (1993)
[Publications] Yokouchi,Y.et al: "Regulatory lnteraction of positional signalings on coordinate expression of homeobox gene in developing limb buds." Progress in Clinical and Biological Research. 383A. 71-78 (1993)
[Publications] Kubo,S.et al: "A novel from of self tolerance dictated in the thymus of trausgenic mice with auto reactive TCR a and b chain genes." Internatl Immunol in press.
[Publications] Watanabe,N.et al: "Parthenogenetic activation of oocytes,but normal spermatogenesis and somatic cell growth,by c-mos-deficiency in mice." Nature in press.
[Publications] Yagi,T.et al: "Fyn expression during neurogenesis in mouse embryos." Oncogene in press.
[Publications] Yagi,T.et al: "A novel ES cell strain,TT2,with high germline-differentioting potency." Anal Biochen. 214. 68-76 (1993)
[Publications] Yagi,T.et al: "Regional localization of Fyn in adult brain;studies with mice in which fyn gene was replaced by lacZ." Oncogene. 8. 3343-3351 (1993)
[Publications] Furuta,Y.et al: "MDS-like experimental myelodys plasia;multilouege abnormal Bematopoies is in transgenic mice horporing the SV40luge Tautigen under on Fg enhaucer." Experimental Hematologg. 21. 806-815 (1993)
[Publications] Nada,S.et al: "Constitutire activation of Src family Kinases in mouse embryos that lack Csk" Cell. 73. 1125-1135 (1993)
[Publications] Imoto,S.et al: "Regulation of class II MHC gene expression by the inducible aut;sence RNA in transgenic mice" Anal Biochen. 210. 231-234 (1993)
[Publications] Yagi,T.et al: "A novel negative selection for houndogous recombinants using diphtheria toxin A fragment gene." Anal Biochen. 214. 77-86 (1993)
[Publications] Tukada,T.et al: "Enhauced prdiferative potential in celture of cells from p53-deficient mice." Oncogene. 8. 3313-3322 (1993)
[Publications] Yagi,T.et al: "A role for Fyn tyrosine Kinase in the suckling behavior of neonatal mice." Nature. 366. 742-745 (1993)
[Publications] Mikoshiba,K.,Okano,H.et al.: "“Molecular genetic analyses of the myelin deficiency and cerebellar ataxia"“Progress in Brain Research"" Elsevier, in press (1994)

1993 Fiscal Year Annual Research Report

発生・形態形式の個体レベルにおける分子生物学的研究

Principal Investigator

竹市 雅俊 京都大学, 理学部, 教授 (00025454)

Research Products

[Publications] Uemura,T.,Shiomi,K.,Takeichi,M.,その他: "Mutation of twins encoding a regulator of protein phosphatase 2A leads to pattern duplication in Drosophila imaginal discs." Genes and Development. 7. 429-440 (1993)

[Publications] Fujimori,T.,Takeichi,M.: "Disruption of epithelial cell-cell adhesion by exogenous expression of a mutated non-functional N-cadherin.21GC02:Molecular Biology of the cell" 4. 37-47 (1993)

[Publications] Oda,H.,Uemura,T.,Takeichi,M.,その他: "Identification of a Drosophila homologue of alpha-catenin and its association with the armadillo protein." Journal of Cell Biology. 121. 1133-1140 (1993)

[Publications] Redies,C.,Takeichi,M.: "Expression of N-cadherin mRNA during development of the mousebrain." Developmental Dynamics. 197. 26-39 (1993)

[Publications] Matsunami,H.,Miyatani,S.,Takeichi,M.,その他: "Cell binding specificity of mouse R-cadherin and chromosomal mapping of the gene." Journal of Cell Science. 106. 401-409 (1993)

[Publications] Watabe,M.,Matsumoto,K.,Takeichi,M.,その他: "Effect of hepatocyte growth factor on cadherin-mediated cell-cell adhesion." Cell Structure and Function. 181. 117-124 (1993)

[Publications] Uchida,N.,Shimamura,K.,Takeichi,M.,その他: "MousealphaN-catenin,two isoforms,specific expression in the nervous system and chromosomal localization of the gene." Developmental Biology. in press. (1994)

[Publications] Okada,T.S.,Yasuda,K.: "How are non-lenticular cells ready for transdifferentiation?" Developmental Dynamics. 196. 273-275 (1993)

[Publications] Kitamura,M.,Miyauchi,K.,Yasuda,K.: "Purification and immunological analyses of a nuclear factor,alphaCE1,that binds to a lens-specific enhacer of the chicken alphaA-crystallin gene." Nucleic Acids Research. accepted. (1994)

[Publications] Niwa,H.et al.: "Anefficient gene-trap method using poly A trap vectors and characterization of gene-trap events." J Biochem. 113. 343-349 (1993)

[Publications] Yamamura,K.et et al: "Transgenic mouse model for human genetic diseases" Mol.Reprod.Dev.36. 248-250 (1993)

[Publications] Pierce,D.F.et al: "Inhlbltlon of mammary duct development but not alveolar outgrowth during pregnancy In MMTV-TGFbeta1s223/225 transgenic mice." Gene&Development. 7. 2308-2317 (1993)

[Publications] Coffey,R.J.et al: "Acceleratlon of mammary neoplasia in virgrln mouse mammary tumor virus enhancer /promotor-transformng growth factor alphatransgenic mice by 7,12 dlmethylbenzanthracene." Caner Research. (1994)

[Publications] 松居靖久: "始原生殖細胞由来の細胞株の胚幹細胞としての性質" 日本疾患モデル学会記録. 9. 9-14 (1993)

[Publications] 松居靖久: "始原生殖細胞株の樹立とその性質" Tissue Culture Research Communications. 12. 273-278 (1993)

[Publications] Sawai,S.et al.: "Defects of embryonic organogenesis resulting from targeted distruption of the N-myc gene in the mouse." Development. 117. 1445-1455 (1993)

[Publications] Kamachi,Y.,Konodoh,H.: "Overlapping positive and negative elements determine lens specificity of the delta1-crystallin enhancer." Molecular and Celluar Biology. 13. 5206-5213 (1993)

[Publications] Funahashi,J.et el: "delta-Crystallin enhancer binding protein deltaEF1 is a zinc finger-homeodomain protein implicated in post gastrulation embryogenesis." Development. 119. 433-446 (1993)

[Publications] Tomotsune,D.et al.: "A mouse homologue of the Drosophila tumor-suppressor gene 1(2)gl controlled by Hox-C8 in vivo." Nature. 365. 69-72 (1993)

[Publications] Yosikawa,S.,Miyamoto,I.et al: "Isolation of a Drosophila Gene Encoding a Head-Specific Guanylyl cyclase." J.Neurochem. 60. 1570-153 (1993)

[Publications] Kume,S.,Muto,A.et al.: "The Xenopus IP3 Receptor;structure,function and localization in oocytes and eggs." Cell. 73. 555-570 (1993)

[Publications] Xing,W.C.,Okano,H.et al: "repo encodes a glial-specific homeodomain protein required in the Drosophila nervous system." Genes and Development in press.

[Publications] 岡野栄之、澤本和延 ら: "神経細胞の分化と軸策走行を制御するEGFモチーフを持つ新しい分泌性因子・strawberry遺伝子産物。" 神経科学. 32. 162-163 (1993)

[Publications] Koyama,E.et al: "Cooperative actlvation of HoxD homeobox genes by factors from the polarizing region and apical ridge in chick limb morphogenesis." Develop Growth&Differ. 35. 189-198 (1993)

[Publications] Yokouchi,Y.et al: "Regulatory lnteraction of positional signalings on coordinate expression of homeobox gene in developing limb buds." Progress in Clinical and Biological Research. 383A. 71-78 (1993)

[Publications] Kubo,S.et al: "A novel from of self tolerance dictated in the thymus of trausgenic mice with auto reactive TCR a and b chain genes." Internatl Immunol in press.

[Publications] Watanabe,N.et al: "Parthenogenetic activation of oocytes,but normal spermatogenesis and somatic cell growth,by c-mos-deficiency in mice." Nature in press.

[Publications] Yagi,T.et al: "Fyn expression during neurogenesis in mouse embryos." Oncogene in press.

[Publications] Yagi,T.et al: "A novel ES cell strain,TT2,with high germline-differentioting potency." Anal Biochen. 214. 68-76 (1993)

[Publications] Yagi,T.et al: "Regional localization of Fyn in adult brain;studies with mice in which fyn gene was replaced by lacZ." Oncogene. 8. 3343-3351 (1993)

[Publications] Furuta,Y.et al: "MDS-like experimental myelodys plasia;multilouege abnormal Bematopoies is in transgenic mice horporing the SV40luge Tautigen under on Fg enhaucer." Experimental Hematologg. 21. 806-815 (1993)

[Publications] Nada,S.et al: "Constitutire activation of Src family Kinases in mouse embryos that lack Csk" Cell. 73. 1125-1135 (1993)

[Publications] Imoto,S.et al: "Regulation of class II MHC gene expression by the inducible aut;sence RNA in transgenic mice" Anal Biochen. 210. 231-234 (1993)

[Publications] Yagi,T.et al: "A novel negative selection for houndogous recombinants using diphtheria toxin A fragment gene." Anal Biochen. 214. 77-86 (1993)

[Publications] Tukada,T.et al: "Enhauced prdiferative potential in celture of cells from p53-deficient mice." Oncogene. 8. 3313-3322 (1993)

[Publications] Yagi,T.et al: "A role for Fyn tyrosine Kinase in the suckling behavior of neonatal mice." Nature. 366. 742-745 (1993)

[Publications] Mikoshiba,K.,Okano,H.et al.: "“Molecular genetic analyses of the myelin deficiency and cerebellar ataxia"“Progress in Brain Research"" Elsevier, in press (1994)

竹市雅俊京都大学, 理学部, 教授 (00025454)

[Publications] 岡野栄之、澤本和延ら: "神経細胞の分化と軸策走行を制御するEGFモチーフを持つ新しい分泌性因子・strawberry遺伝子産物。" 神経科学. 32. 162-163 (1993)