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Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

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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...
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Notch Signaling Pathway03:14

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Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

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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...
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T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
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T Cell Types and Functions01:24

T Cell Types and Functions

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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
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B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

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The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
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Related Experiment Video

Updated: Apr 21, 2026

Stimulation of Notch Signaling in Mouse Osteoclast Precursors
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A central role for Notch in effector CD8(+) T cell differentiation.

Ronald A Backer1, Christina Helbig1, Rebecca Gentek2

  • 11] Department of Cell Biology and Histology, Academic Medical Center, Amsterdam, the Netherlands. [2] Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands.

Nature Immunology
|October 27, 2014
PubMed
Summary

The signaling receptor Notch directs activated CD8(+) T cells toward terminal effector cell (TEC) fates, crucial for clearing infections like influenza. This discovery reveals Notch as a key regulator of T cell differentiation during immune responses.

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Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
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Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
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Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Activated CD8(+) T cells differentiate into either terminal effector cells (TECs) or memory precursor cells (MPCs).
  • The factors governing this critical cell fate decision remain incompletely understood.

Purpose of the Study:

  • To investigate the role of the Notch signaling pathway in CD8(+) T cell differentiation.
  • To elucidate the molecular mechanisms by which Notch influences TEC and MPC fate determination.

Main Methods:

  • Analysis of gene expression profiles in CD8(+) T cells.
  • Investigation of signaling pathways involving Notch, mTOR, and T-bet.
  • Studies using influenza virus infection models.

Main Results:

  • Notch signaling promotes TEC differentiation and is essential for viral clearance.
  • Notch activation suppresses the MPC-specific gene-expression program.
  • Notch expression is induced by inflammatory signals and IL-2 via mTOR and T-bet, creating a positive feedback loop.

Conclusions:

  • Notch acts as a central regulator, integrating signals to direct CD8(+) T cell differentiation.
  • This mechanism ensures effector T cell responses are tailored to infection severity.