对Wnt无翼信号通路的功能基因组分析
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
Science (New York, N.Y.)
|April 9, 2005
概括
研究人员使用Drosophila.的大规模RNA干扰屏幕确定了238个Wnt通路调节器. 许多已识别的基因具有与疾病相关的人类正义基因,突出显示了保留的Wnt信号作用.
科学领域:
- 发展生物学 发展生物学
- 分子信号传输的方法
- 遗传学 是一个遗传学.
背景情况:
- Wnt-Wingless (Wg) 途径对甲状动物发育至关重要,其失调与人类疾病有关.
- 识别保存信号通路的新型调节者对于理解发育和疾病机制至关重要.
研究的目的:
- 在Drosophila细胞中进行全基因组RNA干扰 (RNAi) 选,以确定Wnt通路的新型调节者.
- 评估已识别的Wnt通路调节者的进化保护和潜在的疾病相关性.
主要方法:
- 在Drosophila细胞中进行了全基因组高通量RNA干扰屏幕,以识别Wnt通路调节者.
- 利用互惠-最佳-爆炸分析来识别选基因的人类正义基因.
- 在Drosophila,哺乳动物细胞和斑马鱼胚胎中进行功能测试,以验证保存的Wnt信号功能.
主要成果:
- 确定了238种潜在的Wnt通路调节者,包括已知的成分和新型基因.
- 发现50%的已识别的基因具有人类的正义基因,大约18%与人类疾病有关.
- 在不同的模型系统中对选定的基因进行了验证,进化保守的Wnt信号功能.
结论:
- 细胞培养中的高通量RNAi屏幕与模型生物验证相结合,提供了快速发现信号通路调节者的方法.
- 这些已识别的基因代表了进一步研究发展和人类疾病中的Wnt信号的宝贵资源.
- 这项研究强调了Wnt通路调节的保存性质及其在发育和病理学方面的重要性.
相关概念视频
03:14Notch 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...
02:54Canonical 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...
01:41Non-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...
03:14Notch 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...
02:54Canonical 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...
01:41Non-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...