Rereはレチノ酸のシグナル伝達といくつかの双方向対称性を制御しています
Gonçalo C Vilhais-Neto1, Mitsuji Maruhashi, Karen T Smith
1Stowers Institute for Medical Research, Missouri 64110, USA.
Nature
|February 19, 2010
まとめ
Rere の突然変異は,レチノ酸のシグナル伝達に影響することで,マウスの胚におけるソミット対称性を破壊する. この発見は,ヒトの脊椎椎病のような脊椎の欠陥を説明するかもしれない.
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:
- 脊椎動物の体平面組織は,双方向の対称性によって特徴付けられています.
- ソミトの形成は,骨格の発達に不可欠であり,正確な対称性が必要です.
- 以前の研究では,ソミット対称性を維持する際にレチノ酸の役割を示していた.
研究 の 目的:
- 胚の発達中のソミット対称性の確立におけるRere遺伝子の役割を調査する.
- Rereがレチノ酸シグナル伝達と左から右のパターンを影響する分子メカニズムを解明する.
- Rere誤調節とヒトの脊髄変形の間の潜在的な関連性を調査する.
主な方法:
- Rere遺伝子に変異があるマウス胚の分析.
- レチノ酸のシグナル伝達経路とFgf8.8との相互作用の調査
- Rere-Nr2f2-p300-レチノ酸受容体複合体を特徴付けるための生化学的分析.
- レチノ酸の標的遺伝子発現への影響を評価するための遺伝子ノックダウン実験.
主要な成果:
- 希少な変異により,マウスの胚で非対称なソミトが形成される.
- Rereは,ソミット対称性を維持するために不可欠なレチノ酸シグナル伝達を調節します.
- Rereは,Nr2f2とp300と相互作用して,レチノ酸の標的遺伝子転写を促進する複合体を形成します.
- Nr2f2の非対称的発現は,レチノ酸シグナル伝達とソミット非対称性の変化と相関する.
結論:
- Rere遺伝子は,レチノ酸のシグナル伝達を調節することにより,ソミット対称性を制御する上で重要な役割を果たします.
- 特定されたレレを含む複合体は,レチノ酸標的の転写活性化に不可欠である.
- この発達メカニズムの不調は,脊椎病を含む先天性脊髄異常に寄与する可能性があります.
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