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Related Concept Videos

Notch Signaling Pathway03:14

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...
Notch Signaling Pathway03:14

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...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

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...
Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...

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A Method for Labeling Vasculature in Embryonic Mice
09:58

A Method for Labeling Vasculature in Embryonic Mice

Published on: October 7, 2011

VEGFRs and Notch: a dynamic collaboration in vascular patterning.

Lars Jakobsson1, Katie Bentley, Holger Gerhardt

  • 1Vascular Biology Laboratory, London Research Institute - Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.

Biochemical Society Transactions
|November 14, 2009
PubMed
Summary

Endothelial cells (ECs) exhibit heterogeneity, regulated by Delta-like 4 (Dll4)/Notch signaling, which controls cell specification during vascular development. Understanding this process is crucial for functional vasculature formation.

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Area of Science:

  • Vascular biology
  • Cell signaling
  • Developmental biology

Background:

  • Endothelial cells (ECs) display significant heterogeneity in morphology, function, and gene expression within developing vasculature.
  • Inter-endothelial communication mediated by Delta-like 4 (Dll4) and Notch signaling is a critical regulator of endothelial heterogeneity.
  • Dll4/Notch signaling controls arterial cell specification and the selection between tip and stalk cell phenotypes during angiogenesis.

Purpose of the Study:

  • To elucidate the precise mechanisms by which Notch signaling inhibits stalk cells from adopting a tip cell fate.
  • To investigate the role of quantitative differences in VEGF receptor (VEGFR) system components, regulated by Notch, in endothelial cell (EC) specification.
  • To understand the integrated processes of endothelial cell specification at a systems level.

Main Methods:

  • Utilizing computational modeling for iterative analysis of the tip versus stalk cell selection process.
  • Integrating computational modeling with experimental observation and validation.
  • Studying mosaic vascular beds composed of genetically modified and wild-type ECs in dynamic interactions.

Main Results:

  • Tip cell formation is the default response to vascular endothelial growth factor (VEGF) during sprouting angiogenesis.
  • The stalk cell phenotype is acquired through Dll4/Notch-mediated lateral inhibition.
  • Notch signaling regulates multiple components of the VEGFR system, suggesting quantitative protein expression differences are key.

Conclusions:

  • Quantitative differences in protein expression within the VEGFR system, influenced by Notch, are likely crucial for functional vasculature development.
  • Investigating mosaic vascular beds offers a powerful approach to dissecting the molecular control and cellular mechanisms of EC specification.
  • Further research into Dll4/Notch signaling and VEGFR regulation will advance our understanding of endothelial heterogeneity and vascular development.