皮質脊髄系の発達と進化のシス調節制御
Sungbo Shim1, Kenneth Y Kwan, Mingfeng Li
1Department of Neurobiology and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Nature
|June 9, 2012
まとめ
研究者らは,皮質脊髄神経細胞の発達を制御する遺伝子調節要素を発見した. この元素,E4はSOX転写因子と相互作用し,哺乳類の適切な脳配線と皮質層形成を保証する.
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
- 進化生物学の進化生物学について
背景:
- 哺乳類の6層の脳新皮質と脊髄皮質は,重要な進化的革新である.
- 新皮質の発達と進化を左右する遺伝的メカニズムは完全に理解されていません.
研究 の 目的:
- 皮質脊髄神経細胞の発達を調節する遺伝的要素を特定する.
- 哺乳類新皮質の規制ネットワークの進化的起源を解明する.
主な方法:
- Fezf2遺伝子の皮質特有の強化剤として機能する保存された非エクソニック要素 (E4) の識別.
- E4元素とのSOX4,SOX11,SOX5の相互作用を分析した.
- Fezf2発現とニューロン発達の影響を評価するために,大脳皮質のSox4とSox11をCRISPR媒介で消去する.
- テトラポッドの進化におけるE4におけるSOX結合部位の比較分析.
主要な成果:
- E4は,Fezf2の重要な強化剤として作用し,Fezf2は,皮質脊髄神経細胞のアイデンティティに不可欠な遺伝子です.
- SOX4とSOX11はE4を活性化し,抑制器SOX5.5と競合する.
- Sox4 と Sox11 の削除は,Fezf2 の発現を妨害し,皮質脊髄神経の特異性を低下させ,リールのような皮質のラミネーションの欠陥を引き起こします.
- 証拠は,四足類と哺乳類の進化の間,E4における機能的なSOX結合部位の進化を示唆しています.
結論:
- SOX転写因子は,Fezf2増強剤E4に収束し,皮質脊髄神経細胞の発達を調節する.
- この規制ネットワークは,神経のアイデンティティ,接続性,皮質構造の確立に不可欠です.
- この発見は,哺乳類の新皮質進化の遺伝的基礎についての洞察を提供します.
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