转录因子Mesp2通过抑制Notch活动来建立细分边界
Mitsuru Morimoto1, Yu Takahashi, Maho Endo
1Division of Mammalian Development, National Institute of Genetics, Mishima, Japan.
Nature
|May 20, 2005
概括
脊椎动物的细分依赖于索米特. 这项研究揭示了Notch活动在后面的前皮层中皮层中振荡,并在前皮层中被捕,通过Mesp2和Lfng形成一些边界.
科学领域:
- 发育生物学是发展生物学.
- 胚胎发生是胚胎发生.
- 分子生物学分子生物学
背景情况:
- 脊椎动物的细分包括索米特的形成.
- "时钟和波面"模型通过Notch信号振荡来解释一些周期性.
- 缺少诺奇振荡及其转化为细分模式的直接证据.
研究的目的:
- 在小鼠胚胎发生过程中可视化内源的Notch1活动动态.
- 阐明索米特边界形成的机制.
- 调查Mesp2和Lfng在翻译Notch振荡中的作用.
主要方法:
- 在小鼠内源性Notch1活动的体内可视化.
- 对诺奇信号元件的基因操纵.
- 对基因相互作用的生物化学分析.
主要成果:
- 诺奇1活动在后面的前额膜间皮 (PSM) 中振荡.
- 在前PSM中,Notch1活动被阻止,形成波浪.
- 索米特边界在激活和抑制的Notch1域的接口上形成.
- 通过诱导Lfng,Mesp2抑制了Notch活动,从而创建了这个接口.
结论:
- 这项研究提供了直接证据,证明了在索米特形成过程中振荡和停止的Notch活动.
- Mesp2诱导的Lfng介导时间的Notch振荡转化为空间的somite边界.
- 这种机制澄清了"时钟和波"模型如何产生脊椎动物的超级结构.
相关概念视频
RNA Polymerase II Accessory Proteins
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
Master Transcription Regulators
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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 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...
Hedgehog 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...
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 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...
Role 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...


