GPR56の進化的にダイナミックな代替スプライシングは,地域の脳皮質のパターンを調節する
Byoung-Il Bae1, Ian Tietjen, Kutay D Atabay
1Division of Genetics and Genomics, Manton Center for Orphan Disease, and Howard Hughes Medical Institute, Boston Children's Hospital, Broad Institute of MIT and Harvard, and Departments of Pediatrics and Neurology, Harvard Medical School, Boston, MA 02115, USA.
Science (New York, N.Y.)
|February 18, 2014
まとめ
GPR56遺伝子の調節要素の突然変異は,人間の脳の発達を妨げ,特に言語領域に影響します. この発見は,新皮質の進化と脳形成における遺伝子調節に光を当てています.
科学分野:
- 神経科学は神経科学である.
- 発達生物学 発達生物学について
- 遺伝学 遺伝学とは
背景:
- 人間の新皮質における特化した機能領域の形成は十分に理解されていません.
- GPR56 (Gタンパク質結合受容体56) は,正常な皮質発達に不可欠であり,皮質の原始細胞で発現する.
- GPR56発現レベルは,原始細胞の増殖に影響を与えます.
研究 の 目的:
- GPR56の規制要素の特定の突然変異がヒトの皮質発達に与える影響を調査する.
- この突然変異が遺伝子発現と転写因子結合にどのように影響するかを理解する.
- 新皮質の進化に及ぼす影響を調査する.
主な方法:
- GPR56の規制要素で15塩基対の削除変異を特定しました.
- 人間の皮質におけるGPR56発現に対する突然変異の影響を分析した.
- RFX転写因子結合の障害を調査した.
- GPR56のスプライス形態と,種間の規制要素を比較した.
主要な成果:
- 変異は,ブロカの領域を含むシルビア裂け目を囲む人間の皮質を選択的に破壊した.
- この障害は,地域的なGPR56発現が変化し,RFX転写因子結合が阻害されたことによって引き起こされた.
- GPR56のスプライス形態と規制要素は,マウスとヒトの間で有意な変化を示しています.
- 旋脳哺乳類の調節要素は,制限された側側皮質発現を誘導する.
結論:
- 代替プロモーターによるGPR56発現パターンの制御は,幹細胞の増殖と脳折り畳み (ギラルパターニング) に影響を与えます.
- このメカニズムは,新皮質の進化に役割を果たす可能性がある.
- この研究は,地域の新皮質の発達と進化の基礎となる分子機構を明らかにしています.
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