可归因于FOXC1的表型中的类型包括改变的状和依赖于状的信号传递
Serhiy Havrylov1,2, Paul Chrystal1,2, Suey van Baarle1,2
1Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada.
Scientific reports
|August 31, 2024
概括
叉头转录因子FOXC1的改变会影响毛的长度和信号,从而导致阿克森菲尔德-里格综合征的表型. 这项研究揭示了FOXC1的存在.
科学领域:
- 分子生物学分子生物学
- 发展生物学 发展生物学
- 遗传学 遗传学是一种遗传学.
背景情况:
- 毛是关键的细胞结构,参与各种信号通路.
- 功能障碍的乳毛会导致一系列严重的人类疾病,称为乳毛病.
- 纤毛发育的转录调节及其在FOXC1相关疾病中的作用尚未完全理解.
研究的目的:
- 调查毛介导信号在与FOXC1.1相关的多种表型中的作用.
- 为了确定FOXC1是否直接影响乳毛结构和功能.
主要方法:
- 对FOXC1相关的阿森菲尔德-里格综合征 (ARS) 患者的纤毛病相关表型的分析.
- 在体外操纵Foxc1蛋白水平 (shRNA,CRISPR/Cas9,过度表达) 以评估对毛长度的影响.
- 评估依赖于毛的信号通路 (刺,PDGFRα) 和 Gli2 的定位.
- 使用小鼠胚胎脑膜进行体内研究,以评估Foxc1突变物中的毛长度和基因表达.
主要成果:
- 与FOXC1相关的ARS患者表现出高频率的纤毛病相关的表型.
- 改变Foxc1水平在体外和体内显著改变毛长度.
- 福克斯c1操纵扰乱了 (Hh) 和PDGFRα信号通路,包括Gli2区分.
- 在小鼠脑膜中Foxc1缺乏导致小毛长度减少和Hh和Pdgfrα通路组件的表达失调.
结论:
- FOXC1在调节乳毛长度和功能方面发挥着至关重要的作用.
- 改变的纤毛介导信号,特别是Hh和PDGFRα通路,有助于FOXC1相关的表型.
- 这项研究提供了FOXC1,乳毛功能障碍和疾病发病之间的机械联系.
相关概念视频
01:33Pleiotropy
40.3K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
40.3K
01:22Microtubules in Signaling
1.7K
The primary cilium, made up of microtubules, acts as antennae on the cell surfaces for relaying external stimuli into the cells. These fine hair-like structures are present, generally one per cell. These are non-motile cilia in a 9+0 microtubules arrangement, where the central pair of microtubules are absent. The primary cilia arise from the basal body embedded in the cell membrane. Intraflagellar transport (IFT) carries requisite proteins from the cytoplasm to the cilium because the primary...
1.7K
02:33Hedgehog Signaling Pathway
7.3K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.3K
01:39Epistasis
46.5K
In addition to multiple alleles at the same locus influencing traits, numerous genes or alleles at different locations may interact and influence phenotypes in a phenomenon called epistasis. For example, rabbit fur can be black or brown depending on whether the animal is homozygous dominant or heterozygous at a TYRP1 locus. However, if the rabbit is also homozygous recessive at a locus on the tyrosinase gene (TYR), it will have an unshaded coat that appears white, regardless of its TYRP1...
46.5K
03:14Notch Signaling Pathway
4.2K
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...
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...
4.2K
01:05Mechanism of Ciliary Motion
3.6K
The ciliary structures were first seen in 1647 by Antonie Leeuwenhoek while observing the protozoans. In lower organisms, these appendages are responsible for cell movement, while in higher organisms, these appendages help in the movement of the extracellular fluids within the body cavities.
The cilia are made up of microtubules in a 9+2 arrangement, with nine microtubule doublet ring bundles, surrounding a pair of central singlet microtubule bundles. The doublet microtubule bundles are...
The cilia are made up of microtubules in a 9+2 arrangement, with nine microtubule doublet ring bundles, surrounding a pair of central singlet microtubule bundles. The doublet microtubule bundles are...
3.6K