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胚の発達中のFGFシグナリングは,多様な表皮におけるシリアの長さを調節する
Judith M Neugebauer1, Jeffrey D Amack, Annita G Peterson
1Department of Neurobiology and Anatomy, University of Utah School of Medicine, Eccles Institute of Human Genetics, Building 533, Room 3160, 15 North 2030 East, Salt Lake City, Utah 84112-5330, USA.
Nature
|February 27, 2009
まとめ
線維細胞成長因子 (FGF) 信号伝達は,脊椎動物の胚発達におけるの長さと機能を調節するために重要である. この経路は,イントラフラジェラ輸送遺伝子に影響を与え,様々な組織に影響を与えることで,シリアの長さを制御します.
科学分野:
- 細胞生物学 細胞生物学
- 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.
背景:
- シリアは,胚の発達と細胞シグナル伝達に関与する重要な細胞表面器官である.
- シリアの長さを制御する細胞-細胞の信号伝達経路は,ほとんど不明のままである.
研究 の 目的:
- 繊維芽生殖成長因子 (FGF) のシグナル伝達がシリアの長さと機能を調節する役割を調査する.
- FGFシグナル伝達によってシリアの長さを制御する分子メカニズムを解明する.
主な方法:
- FGF受容体1 (Fgfr1) のモルフォリノノ・ノックダウンがゼブラフィッシュとクセノプスの胚に存在する.
- 支配的ネガティブなFGF受容体 (DN-Fgfr1) の発現
- SU5402.2を使用したFGFシグナリングの薬理学的阻害
- シリアの長さ,液体の流れ,および遺伝子発現の分析 (foxj1, rfx2, ift88).
主要な成果:
- FGFシグナル伝達阻害 (Fgfr1ノックダウン,DN-Fgfr1,SU5402) は,さまざまな組織 (クッフェルの膀,眼膜膀,プロネフリック管,ガストロコーエルの屋根板) で,一貫してシリアの長さを減少させます.
- ゼブラフィッシュのシリアの長さの縮小 Kupfferの膀は,左-右軸形成に不可欠な方向性流体の流れを混乱させた.
- FGFシグナリングは,Fgf8/Fgf24-Fgfr1-イントラフラゲラ輸送経路経由でシリアの長さを調節し,foxj1,rfx2,ift88発現をダウン調節します.
結論:
- FGFのシグナル伝達は,複数の脊椎動物の組織にわたってシリアの長さを調節する上で,根本的で保存された役割を果たします.
- FGFシグナリングの調節不全は,シリア機能障害による発達障害や疾患に寄与する可能性があります.
- 発見は,FGF媒介の保存された経路を明らかにし,イントラフラゲラ輸送を通じてシリアの長さを制御しています.
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