Fgf/Gremlin阻害フィードバックループは,四肢芽の成長の終了を誘発する
1Laboratory of Genetics, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Nature
|July 3, 2008
まとめ
新しい自己終了回路が臓器のサイズを調節する. 線維芽生殖成長因子 (FGF) 信号伝達は,Gremlin1 (Grem1) を抑制し,肢芽の成長と終結のバランスをとる抑制ループを作成します.
科学分野:
- 発達生物学 発達生物学とは
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- 臓器の形成と再生は,ステレオタイプ的なサイズを達成するために,成長促進および制限信号の正確な制御を必要とします.
- 肢芽の成長は,線維細胞成長因子 (FGF),ソニック・ヘッジホッグ (Shh),およびグレムリン1 (Grem1) を含むポジティブなフィードバックループによって調節されます.
研究 の 目的:
- 末肢の結末のメカニズム,特にマウスの末肢の結末のシグナルの配列を調査する.
- 手足の芽の成長制御のための現在受け入れられているモデルを超えた代替規制メカニズムを特定する.
主な方法:
- FGF/Shh/Grem1陽性フィードバックループ内の遺伝子が欠けている化合物マウス変異体の分析.
- 信号伝達経路間の新しい規制相互作用を特定するための遺伝子分析.
主要な成果:
- FGFシグナル伝達がGremlin1 (Grem1) 発現を抑制し,新しいFGF/Grem1阻害ループを確立することを実証しました.
- この抑制は,高いFGF活動に依存し,マウスとチキの両方の肢芽に発生します.
- 発見は,自己促進 (陽性FGF/Shhループ) と自己終結 (FGF/Grem1阻害ループ) の回路が成長を制御していることを明らかにしています.
結論:
- 新しいFGF/Grem1阻害ループは,陽性FGF/Shhループと協調して,四肢の芽のサイズを制御します.
- この自己調節回路は,異なる種で観察されたパターンと一致する方法で成長信号の終了を保証します.
- 特定された回路は,多様な発達および再生の文脈で組織サイズ調節を理解するための枠組みを提供します.
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