在组织形态发生过程中对刺线路抑制的上下文依赖的状调节
Sun-Hee Hwang1, Kevin Andrew White1, Bandarigoda Nipunika Somatilaka1,2
1Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
PLoS genetics
|November 9, 2023
概括
主要毛通过控制鹿通路中的GLI激活剂和抑制剂来调节组织发育. 这项研究揭示了GLI效应器控制的不同模式,对于小鼠神经管和骨发育至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 发展生物学 发展生物学
- 遗传学 遗传学 是一个
背景情况:
- 组织形态发生依赖于亚细胞信号传递,主要的乳毛在隔离信号通路中发挥着关键作用.
- 刺通路利用GLI转录因子,产生激活剂 (GLI-A) 和抑制剂 (GLI-R),毛是它们形成的必要条件.
- 了解GLI-A/GLI-R如何协调毛调节的形态遗传途径至关重要,但尚未得到充分理解.
研究的目的:
- 确定GLI-A和GLI-R在小鼠发育过程中刺路径脱压导致的表型中的特定要求.
- 研究GPR161和ANKMY2在通过cAMP/蛋白质激酶-A信号传递通过乳头介导的GLI-R生成中的作用.
- 阐明组织形态发生过程中初级毛囊对GLI效应器调节的不同模式.
主要方法:
- 基因表现分析涉及Gpr161,Ankmy2,Gli2/Gli3和Smoothened中的突变物.
- 利用Gpr161状局部化敲进突变来评估独立于状局部化的cAMP信号能力.
- 在小鼠神经管和骨发育中检查的表型.
主要成果:
- 在三种不同的模式表现的依赖性脱抑现象:独家GLI-R损失,独家GLI-A过量或双重调节.
- 这些模式在很大程度上独立于刺路径传感器 Smoothened.
- 一个具有cAMP信号能力的Gpr161突变仅通过GLI-R损失重复表型,突出其关键作用.
结论:
- 这项研究证明了GLI因子在形态发生过程中的复杂,组织特异性要求.
- 主要毛建立了组织特定的GLI-R值,这对于刺路径抑制至关重要.
- 提出了一个框架,以了解组织发育中的多种主要毛产生的信号模式.
相关概念视频
Hedgehog Signaling Pathway
7.4K
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...
7.4K
Microtubules 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
Notch Signaling Pathway
4.3K
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...
4.3K
Cadherins in Tissue Organization
3.0K
The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
Cell Sorting During Development
Cell sorting plays an...
3.0K
Mechanism of Ciliary Motion
3.7K
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...
3.7K
Cytoskeletal Coordination in Cell Migration
4.8K
A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker...
4.8K


