発生・形態形成の個体レベルにおける分子生物学的研究

• 研究課題/領域番号: 09NP0401
• 研究種目: 創成的基礎研究費
• 配分区分: 補助金
• 研究機関: 京都大学
• 研究代表者: 竹市 雅俊 京都大学, 大学院・理学研究科, 教授 (00025454)
• 研究分担者: 高田 慎治 京都大学, 理学部, 助教授 (60206753) ; 能瀬 聡直 岡崎国立共同研究機構, 基礎生物学研究所, 助手 (30260037) ; 近藤 寿人 大阪大学, 細胞生体工学センター, 教授 (70127083) ; 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) ; 岡野 栄之 大阪大学, 医学部, 教授 (60160694)
• 研究期間 (年度): 1993 – 1997
• 研究課題ステータス: 完了 (1997年度)
• キーワード: 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

研究概要

1.神経系カドヘリンの機能解析を行い、カドヘリン11は海馬のLTPの抑制に関与し、ショウジョウバエDN-カドヘリンは、成虫脳全体のオ-ガニゼーションのために必須であること、などを明らかにした。また、Capriciousについて機能欠失株における運動神経投射パターンなどを解析し、シナプス形成過程における役割を明らかにした。
2.L-Mafの強制発現により外胚葉が水晶体に分化することなどをみつけ、水晶体分化のマスター遺伝子であることを示した。また、頭部側方外胚葉では、眼胞によってSox2/Sox3の発現が誘導され、この領域が水晶体プラコードとなることがわかった。肢芽における異所的なHox発現が、筋肉塊の増殖や順次断裂によるパターン形成を阻害することを示した。Notchの細胞内シグナル機構を探り、Notch→Hes1/Hes5経路の存在を明らかにした。Islet-2機能を阻害した胚では、この遺伝子を発現する感覚神経細胞と運動神経細胞の軸索伸展に特異的な異常が見られた。
マウスエピブラストを、上側と含まない下側に切り分けて初代培養すると、上半分の断片からのみ始原生殖細胞が分化することを明らかにした。Wnt-1/Wnt-3a両遺伝子は神経冠細胞の形成の他に、皮筋節の内側部の形成にも必須であることがわかった。
jmj変異体の表現型を解析し、血球系幹細胞、心筋細胞の発生に深く関わることを示した。胚様体形成をスクリーニング系として、loxPをトラップベクターに組込んだシステムで遺伝子トラップを行なった結果、この方法が極めて効率のよいことが判明した。mouse-musashi-1遺伝子のノックアウトでは、胎生後期に約50%が致死となり、残りの50%は頭部の形態異常やグリア系の細胞の分化異常などの表現型を示した。

研究成果

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