相互连接的信号反环的自我调节系统控制着小鼠的四肢模式
Jean-Denis Bénazet1, Mirko Bischofberger, Eva Tiecke
1Developmental Genetics, Department of Biomedicine, University of Basel, Mattenstrasse 28, CH-4058 Basel, Switzerland.
Science (New York, N.Y.)
|February 21, 2009
概括
声波刺 (SHH) 和纤维细胞生长因子 (FGF) 信号通路调节四肢发育. 骨形态遗传蛋白4 (BMP4) 启动信号传递,SHH 然后通过Gremlin1 (GREM1) 传播,以控制数字形成.
科学领域:
- 发育生物学是发展生物学.
- 分子遗传学 分子遗传学
- 系统生物学 系统生物学
背景情况:
- 胚胎发生依赖于空间上不同的中心之间的复杂信号传输.
- 肢体发育涉及表皮质-介质细胞 (e-m) 反循环,特别是涉及Sonic Hedgehog (SHH),纤维细胞生长因子 (FGF) 和骨形态遗传蛋白 (BMP) 信号.
- 格雷姆林1 (GREM1) 在调解这些反循环中的作用至关重要,但尚未完全阐明.
研究的目的:
- 阐明肢体发育中的e-m反循环的调节机制.
- 了解BMP4,SHH和GREM1在控制数字规范中的相互作用.
- 研究这些信号通路如何形成一个自我调节网络,以促进强壮的肢体发育.
主要方法:
- 利用小鼠分子遗传学研究基因调节.
- 运用数学建模来分析信号动态.
- 研究了Grem1.的差异转录调节.
主要成果:
- BMP4信号发送启动e-m反,随后由SHH传播.
- 一个开关机制将快速的BMP4/GREM1模块连接到较慢的SHH/GREM1/FGF循环.
- 这种相互连接的网络确保了远端四肢发育的稳健调节,适应了变异性.
结论:
- 这项研究揭示了肢体发育中的新型调节开关,涉及BMP4和SHH.
- 一个自我调节的信号网络确保了对数字规格的精确控制.
- 信号通路之间的相互连接在肢体发育过程中提供了弹性和适应性.
相关概念视频
02:33Hedgehog Signaling Pathway
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...
01:07Cell Signaling Feedback Loops
Positive and negative feedback loops are crucial for regulating biological signaling systems. These feedback loops are processes that connect output signals to their inputs.
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop...
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop...
01:18Hierarchy of Motor Control
The hierarchy of motor control refers to the different levels of organization and processing involved in controlling movement in the body. These levels range from higher cortical areas involved in planning and decision-making to lower spinal cord reflexes that respond automatically to external stimuli.
01:31Mechanism of Lamellipodia Formation
Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
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...
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...