Wnt無翼シグナル伝達経路の機能的ゲノム分析
Ramanuj DasGupta1, Ajamete Kaykas, Randall T Moon
1Department of Genetics, Howard Hughes Medical Institute (HHMI), Harvard Medical School, New Research Building, No. 339, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. rdasgupt@genetics.med.harvard.edu
まとめ
研究者らは,ドロソフィラの大規模なRNA干渉スクリーンを用いて238のWnt経路調節体を特定しました. 特定された多くの遺伝子は,疾患に関連したヒトのオートロログを持ち,保存されたWntシグナル伝達役割を強調しています.
科学分野:
- 発達生物学 発達生物学について
- 分子シグナリング
- 遺伝学 遺伝学とは
背景:
- Wnt-Wingless (Wg) 経路は,メタゾアンの発達に不可欠であり,その失調はヒトの病気に関与しています.
- 保存されたシグナル伝達経路の新たなレギュレータを特定することは,発達と疾患のメカニズムを理解するために不可欠です.
研究 の 目的:
- ドロソフィラ細胞で全ゲノムRNA干渉 (RNAi) スクリーンを実施し,Wnt経路の新規レギュレータを特定する.
- 特定されたWnt経路の調節体の進化的保存と潜在的な疾患関連性を評価する.
主な方法:
- ドロソフィラ細胞で全ゲノムにわたる高通量RNA干渉スクリーンを実施し,Wnt経路の調節体を特定しました.
- Reciprocal-Best-Blast分析を使用して,スクリーニングされた遺伝子のヒトオートログを特定しました.
- 保存されたWntシグナル伝達機能を検証するために,ドロソフィラ,哺乳類の細胞,ゼブラフィッシュの胚で機能分析を行った.
主要な成果:
- 既知の成分と新種の遺伝子を含む238の潜在的なWnt経路調節物質を特定しました.
- 特定された遺伝子の50%がヒトのオートロログを持ち,約18%がヒトの疾患に関連していることが判明しました.
- 異なるモデルシステムにおける選択された遺伝子の進化的に保存されたWntシグナル伝達機能を検証した.
結論:
- 細胞培養における高通量RNAiスクリーンは,モデル生物の検証と組み合わせて,シグナル伝達経路の調節体を発見するための迅速な方法を提供します.
- 特定された遺伝子は,開発とヒトの病気におけるWntシグナル伝達に関するさらなる研究のための貴重なリソースを表しています.
- この研究は,Wnt経路調節の保存された性質と,発達と病理学の両方でその重要性を強調しています.
関連する概念動画
Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Canonical Wnt Signaling Pathway
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
Non-Canonical Wnt Signaling Pathways
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Canonical Wnt Signaling Pathway
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
Non-Canonical Wnt Signaling Pathways
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...


