相关实验视频

Updated: Jun 15, 2025

Author Spotlight: Collecting the Brain and Serum from the Same Mice Fetus to Study Brain Tumor Development

Author Spotlight: Collecting the Brain and Serum from the Same Mice Fetus to Study Brain Tumor Development

Published on: May 17, 2024

有害的ZNRF3生殖系变体通过对Wnt/β-catenin信号传递的域特异性影响,导致与镜像大脑表型的神经发育障碍

Paranchai Boonsawat¹, Reza Asadollahi², Dunja Niedrist¹

¹Institute of Medical Genetics, University of Zurich, Zurich, Switzerland.

American journal of human genetics

|August 21, 2024

概括

生殖系ZNRF3变种通过明显的Wnt/β-catenin信号干扰引起神经发育障碍 (NDD). 误解变体导致大脑症或小脑症,而其他变体导致器官问题.

科学领域:

遗传学是一个遗传学.
发育生物学发展生物学
分子生物学分子生物学

背景情况:

和RING手指3 (ZNRF3) 调节Wnt/β-catenin信号传输,对大脑发育至关重要.
生殖系ZNRF3变体以前没有与神经发育障碍 (NDD) 相关.

研究的目的:

调查生殖线ZNRF3变异在NDD和其他表型中的作用.
为了将ZNRF3基因型与观察到的表型相关联,并了解潜在的病理机制.

主要方法:

使用GeneMatcher/Decipher识别了ZNRF3变异的个体.
进行了结构建模和体外转录报告员测试.
评估了对Wnt/β-catenin与Wnt3a和/或RSPO的信号传递的变异效应.

主要成果:

八个具有 de novo missense ZNRF3 变异的个体呈现了 NDD,与与 RING 结合酶域相关的巨脑症.
一个患有小脑NDD的个体在RSPO绑定域中有一个变异.
有截断或删除变异的4个人显示非NDD表型 (心脏,上腺,脏问题).
在RING结合酶域中的Missense变异主要增强了Wnt/β-catenin信号传递,而RSPO结合域变异减弱了它.
与对照组相比,切断/删除变体对Wnt/β-catenin信号传递的影响最小.

结论:

生殖系ZNRF3变种可以通过明显的Wnt/β-catenin信号失调引起具有镜像大脑大小表型 (大脑/小脑) 的NDD.
蛋白质域特定的ZNRF3变异导致不同的病理机制和临床结果.
ZNRF3生殖系变异与NDD和其他器官特异性疾病有关.

关键词:

没有信号发送.在ZNRF3中,上腺功能不全的情况遗传性心脏缺陷遗传性心脏缺陷遗传性心脏缺陷占主导地位的负面影响.简单地说,这是一个简单的缺陷.宏观头脑是什么意思?宏观头脑是什么意思微头症是一个微头症.镜子表型的镜子表型.瘤抑制基因的基因抑制器

更多相关视频

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information

Published on: August 15, 2019

相关概念视频

Canonical Wnt Signaling Pathway

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...

Non-Canonical Wnt Signaling Pathways

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

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...