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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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Hemodialysis I: Introduction01:25

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Hemodialysis (HD) is a medical treatment that artificially removes waste products, excess fluids, and toxins from the blood when the kidneys are no longer able to perform these functions effectively. In this process, blood is filtered through a semipermeable membrane, allowing for the selective removal of waste while preserving necessary components like blood cells and proteins. Hemodialysis is typically performed in patients with end-stage renal disease (ESRD) or severe kidney...
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Regulation of Angiogenesis and Blood Supply01:24

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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...
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Anastomoses

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In human anatomy, anastomosis refers to a connection or opening between two things, particularly between blood vessels or other tubular structures. The term is derived from the Greek term 'anastomosis,' which means 'outlet' or 'opening.' This natural network of connections plays a critical role in the survival and functionality of the human body.
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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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Related Experiment Video

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Comprehensive Endovascular and Open Surgical Management of Cerebral Arteriovenous Malformations
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Context-specific interactions between Notch and ALK1 cannot explain ALK1-associated arteriovenous malformations.

Elizabeth R Rochon1, Daniel S Wright1, Max M Schubert1

  • 1Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.

Cardiovascular Research
|May 14, 2015
PubMed
Summary

Notch and activin receptor-like kinase 1 (ALK1) signaling pathways interact differently in various blood vessels. ALK1 is not essential for arterial identity, and Notch pathway alterations do not explain ALK1-related arteriovenous malformations (AVMs).

Keywords:
Activin receptor-like kinase 1AngiogenesisArteriovenous malformationNotchZebrafish

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Area of Science:

  • Developmental biology
  • Molecular biology
  • Vascular biology

Background:

  • Notch and ALK1 signaling are crucial for blood vessel development, including arterial specification and AVM formation.
  • ALK1 can cooperate with Notch to regulate target genes in endothelial cells, suggesting a collaborative role in arterial programming.

Purpose of the Study:

  • To investigate the interaction between Notch and ALK1 signaling pathways in the developing vertebrate vasculature.
  • To understand the specific roles of Notch and ALK1 in regulating gene expression and vascular morphology.

Main Methods:

  • Modulation of Notch and ALK1 activities in zebrafish embryos.
  • Analysis of Notch target gene expression (e.g., hey2, ephrinb2a, dll4) in the arterial endothelium.
  • Examination of vascular morphology, including AVM development.

Main Results:

  • ALK1 is not essential for Notch target gene expression in arterial endothelium but supports hey2 and ephrinb2a in the dorsal aorta upon loss of Notch signaling.
  • Notch and ALK1 have opposing roles in hey2 and dll4 expression in cranial arteries and arterial endothelium, respectively.
  • While alk1 loss increases dll4 expression, Notch pathway modulation could not replicate or rescue alk1 mutant-associated AVMs.

Conclusions:

  • Control of Notch targets in arterial endothelium is context-dependent, varying by gene and region.
  • ALK1 is not required for establishing arterial identity.
  • AVMs associated with ALK1 mutations are not caused by defective arterial specification or altered Notch signaling.