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08:01
Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
诺奇和德尔塔之间的Cis相互作用产生相互排斥的信号状态
David Sprinzak1, Amit Lakhanpal, Lauren Lebon
1Howard Hughes Medical Institute, Division of Biology and Department of Applied Physics, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA.
Nature
|April 27, 2010
概括
诺奇-德尔塔信号通路使用cis抑制和转激活来进行细胞通信. 这项研究揭示了一种超敏感的开关机制,驱动着发育组织中的模式形成.
科学领域:
- 细胞和发育生物学
- 生物物理学的生物物理.
- 系统生物学 系统生物学
背景情况:
- 诺奇-德尔塔信号通路对于细胞在发育过程中的细胞通信至关重要,它调节细胞命运决策和组织模式.
- 德尔塔配体表现出双重活性:在相邻细胞中转激活Notch,并在同一细胞中抑制cis的Notch.
- 这些双重活动的整合及其在模式形成中的作用仍然不完全理解.
研究的目的:
- 为了研究Notch-Delta信号在单个哺乳动物细胞中的定量动力学.
- 阐明系统如何整合cis和trans-Delta活动以实现模式形成.
- 了解Notch-Delta系统的输入-输出关系.
主要方法:
- 开发一个定量时隔显微镜平台,用于实时分析Notch-Delta信号动态.
- 对 cis 和 trans-Delta 度进行控制的操纵.
- 监控Notch报告员动态,以测量系统的响应.
主要成果:
- 对trans-Delta的隙反应是分级的,而对cis-Delta的反应是尖的和依赖值的.
- 一个数学模型表明,Notch和Delta蛋白的相互无活化会产生一个超敏感的开关.
- 这种开关可以放大细胞之间的差异,形成利的边界和横向抑制模式.
结论:
- 诺奇-德尔塔系统的功能是一种超敏感的开关,通过相互蛋白质无活化促进模式形成.
- 这种机制解释了在发育过程中如何出现尖的边界和横向抑制模式.
- 这些发现提供了对发育过程和以前无法解释的突变现象型的洞察力.
相关概念视频
01:19Contact-dependent Signaling
Contact-dependent signaling, as the name suggests, requires that communicating cells be in direct contact with each other. This is achieved either through receptor-ligand interactions or by specialized cytoplasmic channels that allow the flow of small molecules between cells. In animal cells, channels called gap junctions facilitate contact-dependent signaling in certain tissues, whereas, plasmodesmata perform a similar function in plants.
Gap Junctions
In animal cells, gap junctions are formed...
Gap Junctions
In animal cells, gap junctions are formed...
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...
02:33Hedgehog 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...
01:19Interactions 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...
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...
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...