マイクロRNAmiR-235はブラスト細胞の静止状態を栄養状態に結びつけます
Hidefumi Kasuga1, Masamitsu Fukuyama, Aya Kitazawa
1Laboratory of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033, Japan.
Nature
|May 7, 2013
まとめ
Caenorhabditis elegansのミクロRNAmiR-235はL1ダイアパウスの間に発達を停止し,インスリン/IGFシグナル伝達経路経由で栄養素の可用性に反応する. この研究は,栄養に基づいたブラスト細胞の行動を調節する miR-92 オーソログの新たな役割を明らかにしています.
科学分野:
- 発達生物学 発達生物学について
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- 幹細胞とブラスト細胞の行動は,成長,再生,組織ホメオスタシスに不可欠です.
- Caenorhabditis elegansの幼虫はL1ダイアパスに入り,インスリン/IGFシグナル伝達 (IIS) 経路によって調節される栄養素が利用できるまで開発を停止します.
- IISシグナル伝達と栄養に依存するブラスト細胞の静止状態を結びつける正確なメカニズムは不明である.
研究 の 目的:
- IIS経路が栄養素の利用可能性に応じて発達的な静止状態を調節するメカニズムを解明する.
- ブラスト細胞の行動とC. elegansの栄養状態の結合に関与する重要な分子プレーヤーを特定する.
主な方法:
- C. elegansの発達とL1のダイアパウズにおけるmicroRNA (miRNA) miR-235の役割を調査した.
- 食事とIIS経路活動に対する反応として,mir-235とその標的の発現を分析した.
- 遺伝子解析を用いて,miR-235とその標的であるnhr-91がニューロブラストとメソブラストの調節における機能を評価した.
主要な成果:
- 哺乳類のmiR-92の同型であるmiR-235は,下皮質と膠質細胞に作用し,神経芽細胞とメソ芽細胞の胚後発育を停止します.
- mir-235の発現は,L1ダイアパウスの間に持続し,IIS経路に依存して,餌を与えると減少します.
- miR-235の標的であるnhr-91のアップレギュレーションは,miR-235の機能喪失変異体で観察された欠陥を引き起こす.
結論:
- miR-235は,L1ダイアパウスの間,ブラスト細胞の行動と栄養素の可用性を調整する上で重要な役割を果たします.
- この研究は,栄養状態に基づいて発育停止を媒介する miR-92 矯正医の新しい機能を確立しています.
- 発見は,miRNAとIISシグナル伝達によって制御される発達性可塑性における新しいレギュレーション層を明らかにしています.
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