FGFsが,四肢近辺-遠隔のパターニングに指導的な役割を果たすという遺伝的証拠
Francesca V Mariani1, Christina P Ahn, Gail R Martin
1Department of Anatomy and Program in Developmental Biology, School of Medicine, University of California at San Francisco, San Francisco, California 94158-2324, USA.
Nature
|May 2, 2008
まとめ
アピカル外皮の繊維芽生殖成長因子 (FGF) は,四肢の発達に不可欠である. この研究は,FGF8が十分であることを明らかにしますが,FGFの組み合わせは,以前のモデルに挑戦し,四肢のパターンを指示します.
科学分野:
- 発達生物学 発達生物学について
- 遺伝学 遺伝学とは
- 分子生物学は分子生物学である.
背景:
- アピカル外皮脊 (AER) は,近辺-遠端 (P-D) 軸に沿って四肢の発達のための信号を提供します.
- 線維芽生殖成長因子 (FGFs) は,マウスのAERでFgf4,Fgf8,Fgf9,Fgf17が表現される,AERから派生した重要な信号である.
研究 の 目的:
- マウスの四肢の発達とパターニングにおける特定のAER-FGFの役割を調査する.
- AER-FGFのシグナリングが,四肢のパターニングに指示的か許可的かを判断する.
主な方法:
- AER-FGF遺伝子 (Fgf4,Fgf8,Fgf9,Fgf17) の組み合わせが欠けている複合変異マウスラインの生成と分析.
- ミュータントの肢芽における骨格パターンと遺伝子発現の検査.
主要な成果:
- Fgf4,Fgf9およびFgf17が欠けているマウスの肢体は,Fgf8の充足性を示す,正常な骨格パターンを示しています.
- Fgf8の無活性化だけでは軽度の欠陥を引き起こしますが,他のAER-FGF遺伝子除去と組み合わせると,ますます重度の骨格の現象型につながります.
- AER-FGFは,P-Dパターニングの遺伝子発現と細胞生存を調節し,遠端末領域を特定する指示的な役割を果たします.
結論:
- AER-FGFは,遠端末の領域を指定する上で教科的な役割を果たし,長年にわたる許容的シグナリング仮説に挑戦しています.
- 複数のAER-FGFの組み合わせによる貢献は,正常な肢体の発達とパターン形成に極めて重要です.
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