ノッチとEGFR経路の相互作用は,神経幹細胞の数と自己再生を調節する
Adan Aguirre1, Maria E Rubio, Vittorio Gallo
1Center for Neuroscience Research, Children's National Medical Center, Washington, District of Columbia 20010, USA.
Nature
|September 17, 2010
まとめ
大人の脳における神経幹細胞 (NSC) と神経原始細胞 (NPC) のバランス
科学分野:
- 神経科学は神経科学である.
- 幹細胞生物学 幹細胞生物学
- 細胞シグナル伝達 細胞信号伝達
背景:
- 細胞の微小環境,またはニッチは,自己再生と運命を含む幹細胞の行動を調節する.
- 大人の脳のサブバントリキュラールゾーン (SVZ) には,神経幹細胞 (NSC) と神経原始細胞 (NPC) が宿っている.
- SVZにおけるNSCとNPCのバランスを維持することは,脳の機能と修復に不可欠です.
研究 の 目的:
- 皮膚表皮成長因子受容体 (EGFR) とNotchシグナル伝達経路の相互作用を調査し,SVZニッチ内のNSCとNPCの集団を維持する.
- EGFRとNotchのシグナル伝達相互作用が,成人脳における神経幹細胞と原始細胞のバランスを調節するメカニズムを解明する.
主な方法:
- 成人SVZニッチモデルを用いたインビボ研究.
- EGFRのシグナリングを操作して,NSCとNPCの集団への影響を評価する.
- 細胞と細胞の相互作用と信号経路の交差 (EGFRとNotch) の分析.
主要な成果:
- 強化されたEGFRシグナル伝達 in vivoは,NPCプールの拡大につながります.
- EGFRのシグナル伝達の増加は,NSCの数を減少させ,NSCの自己更新を妨げます.
- この効果は,EGFRシグナリングがNotchシグナリングを調節する非細胞自律的なメカニズムによって媒介されます.
結論:
- EGFRとNotchのシグナル伝達経路の間の新しい相互作用が成人SVZで特定されています.
- このクロストークは,神経幹細胞と原始細胞のバランスを維持するために重要です.
- この発見は,成人の脳におけるNSCとNPCのプール維持を規制する重要なメカニズムを提供する.
関連する概念動画
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...
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...
01:26Stem Cell Niche
The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...
01:19Multipotency of Hematopoietic Stem Cells
The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
01:12Renewal of Skin Epidermal Stem Cells
The skin is divided into epidermis, dermis, and hypodermis, the skin's outermost, middle, and inner layers. The human epidermal layer regularly undergoes renewal, where old, dead cells are replaced by new cells. Epidermal stem cells or EpiSCs divide and differentiate to restore the lost cells. For the renewal process, some EpiSCs continuously self-renew. In contrast, few others differentiate into transit-amplifying cells, which later form prickle or spinous cells, followed by granular cells,...