肝臓発達の開始は,Foxaの転写因子に依存しています

Catherine S Lee¹, Joshua R Friedman, James T Fulmer

¹Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

Nature

|June 17, 2005

まとめ

Foxa1とFoxa2の転写因子は,マウスの肝臓発育に極めて重要です. これらのタンパク質は,前腸内皮の遺伝子発現を調節することによって,細胞の能力を確立し,肝細胞生成を開始します.

科学分野:

発達生物学発達生物学とは
遺伝学遺伝学とは
分子生物学は分子生物学である.

背景:

脊椎動物の肝臓の仕様には,前腸内皮の能力の確立と肝臓特異的な遺伝子の誘導という2つのステップが含まれています.
フォクサ転写因子は,標的遺伝子の染色体構造を変更することによって,能力を確立すると仮定されています.

研究の目的:

マウス胚における肝臓特異化におけるFoxa1とFoxa2の役割を調査する.
foxa1とfoxa2が前腸内皮の能力の確立と肝臓生成の開始に必要かどうかを判断する.

主な方法:

前腸内皮のFoxa1およびFoxa2に欠けているマウス胚の分析.
フィブロブラスト成長因子2 (FGF2) の欠陥のある内皮のインビトロ培養.
アルファフェトタンパク質 (Afp),アルバミン,トランスチレチンなどの肝臓の主要なマーカーの肝芽形成と発現の評価.

主要な成果:

前腸内皮にFoxa1とFoxa2の両方が欠けている胚は,肝芽の発達を示せず,アルファ-フェトタンパク質の発現を失いました.
Foxa1 / Foxa2欠乏した内皮は,FGF2.2で治療された場合でも,アルバミンとトランスチレチンを発現できませんでした.
これらの発見は,早期肝臓発育におけるFoxa1とFoxa2の重要な協力的役割を示しています.

結論:

Foxa1とFoxa2は,前皮内皮における能力を確立するために協調して行動する.
これらの転写因子は,肝臓生成の開始と肝臓特異性の重要な遺伝子の発現に不可欠です.

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