POUドメイン因子による皮質ニューロン移動の転写制御
Robert J McEvilly1, Marcela Ortiz de Diaz, Marcus D Schonemann
1Howard Hughes Medical Institute, Department and School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92037-0648, USA.
Science (New York, N.Y.)
|February 23, 2002
まとめ
転写因子Brn-1とBrn-2は,ニューロン移動を制御することによって,皮質の発達を調節する. その欠如は,脳構造の深刻な欠陥,特にマウスの皮質の逆転につながる.
科学分野:
- 神経科学は神経科学である.
- 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:
- 哺乳類の脳皮質の適切なラミネーションは,認知機能にとって極めて重要です.
- キナーゼCdk5とリガンドリエリンは,皮質の発達経路を媒介することが知られている.
- 皮質発達の分子メカニズムを理解することは,現在進行中の研究分野です.
研究 の 目的:
- Cdk5媒介の皮質ラミネーションの主要な調節体を特定する.
- 前頭脳の発達におけるクラスIIIのPOUドメイン転写因子Brn-1とBrn-2の役割を調査する.
- Brn-1とBrn-2がニューロン移動と皮質の発達を制御する分子メカニズムを解明する.
主な方法:
- マウスモデルにおけるBrn-1およびBrn-2機能の遺伝子解析.
- Cdk5規制サブユニット (p35およびp39) の遺伝子発現の分析.
- 野良型とノックアウト型マウスにおける皮質のレイミネーションとニューロン移動の検査.
主要な成果:
- Brn-1とBrn-2は,ほとんどの層II-Vの皮質ニューロンで共発現する.
- Brn-1とBrn-2は,移動するニューロンにおけるp35とp39の細胞自律的発現を冗長的に調節する.
- Brn-1(-/-) /Brn-2(-/-) マウスは,皮質の逆転として知られる重度の皮質変形を示しています.
- これらの転写因子は,皮質の発達中に放射性移動の開始を決定的に制御する.
結論:
- Brn-1とBrn-2は,Cdk5媒介の皮質ラミネーションの重要なレギュレーターである.
- これらの要因は,皮質ニューロンの放射線移動を開始する上で,重要で冗長な役割を果たします.
- Brn-1およびBrn-2機能の障害は,大脳皮質の発達に重大な欠陥をもたらします.
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