Mesp2転写因子は,Notchの活動を抑制することによって,セグメントの境界を確立します
Mitsuru Morimoto1, Yu Takahashi, Maho Endo
1Division of Mammalian Development, National Institute of Genetics, Mishima, Japan.
Nature
|May 20, 2005
まとめ
脊椎動物のセグメンテーションは,ソミットに依存しています. この研究は,Notchの活動が後部プレソミティックメソデームで振動し,前部で停止し,Mesp2とLfng経由でソミット境界を形成することを明らかにしています.
科学分野:
- 発達生物学 発達生物学とは
- 胚形成とは,胚の形成である.
- 分子生物学は分子生物学である.
背景:
- 脊椎動物のセグメンテーションには,ソミトの形成が含まれています.
- "クロック・アンド・ウェーブフロント"モデルは,ノッチ信号振動によるソミテ周期性を説明する.
- ノッチ振動とそれをセグメンタルパターンに変換する直接的な証拠は存在しない.
研究 の 目的:
- ネズミの胚形成中の内生的なNotch1活動ダイナミクスを視覚化するために.
- ソミット境界形成のメカニズムを解明する.
- ノッチ振動の翻訳におけるMesp2とLfngの役割を調査する.
主な方法:
- ネズミの内生ノッチ1活性のインビボ視覚化.
- Notchのシグナリングコンポーネントの遺伝子操作.
- 遺伝子相互作用の生化学分析.
主要な成果:
- Notch1の活動は,後部プレソミティックメソダーム (PSM) で振動する.
- Notch1の活動は,前側のPSMで停止され,波面を形成します.
- ソミット境界は,活性化されたノッチ1ドメインと抑制されたノッチ1ドメインのインターフェイスで形成されます.
- Mesp2は,Lfngを誘導してNotchの活動を抑制し,このインターフェイスを作成します.
結論:
- この研究は,ソミット形成中に振動し,ノッチ活動を停止した直接的な証拠を提供します.
- Mesp2誘発のLfngは,時的ノッチ振動を空間的ソミット境界に変換することを媒介する.
- このメカニズムは",クロックとウェーブフロント"モデルが脊椎動物のメタメリックス構造をどのように生成するかを明らかにします.
関連する概念動画
02:36RNA 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...
02:23Master 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...
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...
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...