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Notch Signaling Pathway

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...

Notch Signaling Pathway

Notch Signaling Pathway

Role Of Notch Signalling In Intestinal Stem Cell Renewal

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 Heart

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...

Chambers of the Heart

Chambers of the Heart

The human heart is a complex organ made up of four chambers: the right and left atria and the right and left ventricles. These internal chambers are separated by partitions known as the interatrial and interventricular septa. The exterior of the heart features a groove known as the coronary sulcus that demarcates the atria from the ventricles, while the anterior and posterior interventricular sulci distinguish between the two ventricles.
Deoxygenated blood from the body is received in the right...

Regulation of Stroke Volume

Regulation of Stroke Volume

The regulation of stroke volume, which is the amount of blood the heart pumps out during each heartbeat, is critical for maintaining a healthy circulatory system. Stroke volume is influenced by three main factors: preload, contractility, and afterload.
Preload refers to the degree of stretch on the heart before it contracts. It's analogous to the stretching of a rubber band; the more it's stretched, the more forcefully it snaps back. This concept is encapsulated in the Frank-Starling law of the...

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Related Experiment Video

Updated: Mar 29, 2026

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Sequential Notch activation regulates ventricular chamber development.

Gaetano D'Amato¹, Guillermo Luxán¹, Gonzalo del Monte-Nieto¹

¹Intercellular Signalling in Cardiovascular Development &Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.

Nature Cell Biology

|December 8, 2015

Summary

This summary is machine-generated.

Notch signaling orchestrates heart chamber development. Temporal regulation of manic fringe (MFng) and Notch ligands by endocardial cells ensures proper trabeculation and ventricular maturation, preventing heart defects.

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Area of Science:

Cardiovascular Biology
Developmental Biology
Molecular Signaling

Background:

Ventricular chambers are vital for heart function, and their congenital abnormalities lead to severe heart defects.
The precise mechanisms governing the formation and maturation of ventricular chambers from early trabecular meshwork remain unclear.

Purpose of the Study:

To elucidate the role of Notch signaling in the development of heart chambers.
To investigate the temporal regulation of Notch signaling pathways in ventricular development.

Main Methods:

Utilized genetic manipulation to study the function of manic fringe (MFng) and Notch ligands (Dll4, Jag1, Jag2) in cardiac development.
Analyzed the interplay between endocardial and myocardial cells during heart chamber formation.

Main Results:

Notch signaling, modulated by MFng, is crucial for initial trabeculation via Dll4-Notch1.
Ventricular maturation and compaction depend on the downregulation of MFng and Dll4, enabling Jag1/Jag2-Notch1 signaling.
Disruption of this signaling balance severely impairs heart chamber formation.

Conclusions:

A precise temporal sequence of Notch ligand signaling, regulated by MFng, is essential for normal heart chamber development.
This study reveals novel insights into the pathogenesis of cardiomyopathies and provides a foundation for future research.