Tbx6に依存するSox2調節は,軸性幹細胞のニューラルまたはメソダーマの運命を決定する
Tatsuya Takemoto1, Masanori Uchikawa, Megumi Yoshida
1Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan.
Nature
|February 19, 2011
まとめ
Tbx6タンパク質は,胚の発達における細胞の運命決定を制御する. Sox2遺伝子の活動を抑制し,軸性幹細胞が神経組織ではなくパラキシアルメソダーマに発展することを保証します.
科学分野:
- 発達生物学 発達生物学について
- 幹細胞生物学 幹細胞生物学
- 分子遺伝学 分子遺伝学
背景:
- クラシックモデルでは,ニューラルプレートの発達が,エクトダーマからのみ発生することを提案しています.
- 最近の研究では,ニューラル・プレートとパラキシアル・メソデルマの共通のバイポテンシャル軸性幹細胞を明らかにしています.
- Tbx6ヌル突然変異者は子宮外神経管を現しており,神経対中皮の運命選択における役割を示唆しています.
研究 の 目的:
- Tbx6がニューラル対メソダーマルの運命選択を制御する規制メカニズムを解明する.
- 軸性幹細胞の分化中にSox2発現を調節するTbx6の役割を調査する.
主な方法:
- Tbx6ゼロ変異マウス胚の分析.
- 細胞系追跡実験. 細胞系追跡実験.
- Sox2とその強化剤N1.1.の遺伝子発現分析
- CRISPR媒介の増強剤-N1の削除は,変異した胚で.
- 野生型胚のSOX2トランスゲンの誤った発現.
主要な成果:
- Tbx6は,発達中のパラキシアルメソダームにおける強化剤N1の活動を通じてSox2を抑制する.
- Tbx6変異体では,持続的な増強剤N1の活動により,子宮外Sox2の発現と神経管の形成が起こります.
- Tbx6変異体における増強剤N1の削除は,パラキシアルメソダームの発達を救います.
- このプロセスには,Wnt3aのTbx6依存抑制が関与しています.
結論:
- Tbx6は,軸性幹細胞の運命を決定する重要な調節体です.
- Tbx6は,強化剤N1.1を通じてSox2を抑制することによって,パラキシアルメソダームの特異性を促進する.
- このメカニズムは,メソダーマ前駆体からの子宮外神経発達の予防に極めて重要です.
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