脊椎動物における心臓回路を左右する信号経路
Oscar H Ocaña1, Hakan Coskun1, Carolina Minguillón2
1Instituto de Neurociencias (CSIC-UMH), Avenida Ramón y Cajal, s/n, Sant Joan d'Alacant, Alicante, Spain.
Nature
|September 8, 2017
まとめ
新しい研究では 骨型遺伝タンパク質 (BMP) のシグナル伝達が 斑馬魚の胚に 右側非対称性を確立する方法を明らかにしました この経路はPrrx1aを活性化させ 心臓の適切な発達と 左から右の身体のパターンを決定する 細胞の異動を促します
科学分野:
- 発達生物学
- 胚科
- 分子生物学
背景:
- 脊椎動物は 臓器機能に不可欠な内部の左-右非対称性を表していますが 右側アイデンティティを確立するメカニズムはまだ不明です
- 左側特異的な Nodal-Pitx2 経路は知られていますが,右側並行的な指示経路はあまり理解されていません.
- ほとんどの動物の外側対称性は 発達に不可欠な複雑な内側対称性を隠しています
研究 の 目的:
- 脊椎動物の胚の発達における左/右 (L/R) 非対称性の基礎となる分子機構を調査する.
- 胚形成過程で右側に特異的な情報を提供する経路を特定する.
- 心循環とL/RパターンにおけるPrrx1aの役割を解明する.
主な方法:
- L/R非対称性を研究するためのモデル生物としてゼブラフィッシュを使用した.
- Prrx1aの活性化における骨形態遺伝タンパク質 (BMP) 信号伝達の役割を調査した.
- 遺伝子操作 (Prrx1aのダウンレギュレーション) を使用し,心臓の発達への影響を観察した.
- 鶏とマウスの胚で保存されたメカニズムを調べた.
主要な成果:
- BMPのシグナリングは,横板メソダーマのPrrx1aを非対称的に活性化し,右側のレベルがより高いことが示されました.
- Prrx1aは,アクトミオシンに依存するメカニズムを通じて左向きの心臓の移動を誘導する.
- Prrx1aのダウンレギュレーションが 心循環に欠陥をもたらし,メソカルディアを引き起こすことがわかりました.
- Pitx2とPrrx1の転写因子に収束する並列で相互抑制されたノダルとBMP経路を特定した.
結論:
- 左-右の表皮細胞-メゼンキマ移行 (EMT) は,主に右から,心側運動を誘導する非対称な細胞運動と力を発生させる.
- この研究は,心臓発達のL/R不対称性を確立するBMP-Prrx1aとNodal-Pitx2経路を含む保存されたメカニズムを発見した.
- この研究は,脊椎動物の胚の臓器の位置づけと機能を制御する基本的なプロセスに関する新しい洞察を提供します.
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