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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...
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...
Development of the Heart01:27

Development of the Heart

The development of the human heart, a crucial organ, commences from the mesoderm on the 18th or 19th day after fertilization. This process initiates in the cardiogenic area, a group of mesodermal cells at the embryo's head end, which evolves into elongated strands known as cardiogenic cords. These cords undergo a transformation to form hollow-centered endocardial tubes.
As the embryo undergoes lateral folding, these paired tubes approach each other, merging into a single primitive heart tube by...
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...
Determination01:51

Determination

During embryogenesis, cells become progressively committed to different fates through a two-step process: specification followed by determination. Specification is demonstrated by removing a segment of an early embryo, “neutrally” culturing the tissue in vitro—for example, in a petri dish with simple medium—and then observing the derivatives. If the cultured region gives rise to cell types that it would normally generate in the embryo, this means that it is specified. In contrast, determination...

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En Face Endocardial Cushion Preparation for Planar Morphogenesis Analysis in Mouse Embryos
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Notch signaling is essential for ventricular chamber development.

Joaquín Grego-Bessa1, Luis Luna-Zurita, Gonzalo del Monte

  • 1Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/CSIC, Darwin 3, Campus de Cantoblanco, E-28049 Madrid, Spain.

Developmental Cell
|March 6, 2007
PubMed
Summary

Notch signaling in the developing heart is essential for ventricular trabeculation. This pathway regulates cardiomyocyte proliferation and differentiation, critical for preventing congenital heart disease.

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Area of Science:

  • Cardiovascular Biology
  • Developmental Biology
  • Molecular Genetics

Background:

  • Ventricular chamber morphogenesis, including trabeculae formation, is vital for embryonic development and cardiac function.
  • This process relies on intricate cellular crosstalk between the endocardium and myocardium.
  • Disruptions in these early developmental events can lead to congenital heart disease.

Purpose of the Study:

  • To investigate the role of Notch1 signaling in ventricular trabeculation.
  • To identify downstream targets of Notch1 involved in cardiac development.
  • To elucidate the mechanisms by which Notch1 regulates cardiomyocyte proliferation and differentiation.

Main Methods:

  • Utilized Notch1 and RBPJk mutant models in embryonic studies.
  • Performed molecular analyses to assess gene expression and signaling pathways (EphrinB2, NRG1, BMP10).
  • Conducted in vitro culture experiments with exogenous BMP10 and NRG1 to rescue mutant phenotypes.

Main Results:

  • Notch1 activity is concentrated in the presumptive trabecular endocardium.
  • Mutants lacking Notch1 or RBPJk exhibited impaired trabeculation and altered expression of key cardiac markers.
  • Notch signaling directly regulates EphrinB2, which acts upstream of NRG1, influencing cardiomyocyte differentiation.
  • BMP10 independently promotes myocardial proliferation, while NRG1 supports differentiation.

Conclusions:

  • Notch signaling plays a dual role in ventricular trabeculation, independently controlling cardiomyocyte proliferation via BMP10 and differentiation via NRG1.
  • Proper regulation of these processes by Notch is crucial for normal heart development.
  • Perturbations in Notch-mediated signaling during trabeculation may contribute to congenital heart defects.