Related Experiment Video
Updated: Dec 15, 2025

En Face Endocardial Cushion Preparation for Planar Morphogenesis Analysis in Mouse Embryos
Published on: July 27, 2022
NOX2 Is Critical to Endocardial to Mesenchymal Transition and Heart Development
Hoda Moazzen1,2, Yan Wu1,3, Anish Engineer1
1Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, Canada.
Abstract:
NADPH oxidases (NOX) are a major source of reactive oxygen species (ROS) production in the heart. ROS signaling regulates gene expression, cell proliferation, apoptosis, and migration. However, the role of NOX2 in embryonic heart development remains elusive. We hypothesized that deficiency of Nox2 disrupts endocardial to mesenchymal transition (EndMT) and results in congenital septal and valvular defects. Our data show that 34% of Nox2 neonatal mice had various congenital heart defects (CHDs) including atrial septal defects (ASD), ventricular septal defects (VSD), atrioventricular canal defects (AVCD), and malformation of atrioventricular and aortic valves. Notably, Nox2 embryonic hearts show abnormal development of the endocardial cushion as evidenced by decreased cell proliferation and an increased rate of apoptosis. Additionally, Nox2 deficiency disrupted EndMT of atrioventricular cushion explants ex vivo. Furthermore, treatment with N-acetylcysteine (NAC) to reduce ROS levels in the wild-type endocardial cushion explants decreased the number of cells undergoing EndMT. Importantly, deficiency of Nox2 was associated with reduced expression of Gata4, Tgfβ2, Bmp2, Bmp4, and Snail1, which are critical to endocardial cushion and valvoseptal development. We conclude that NOX2 is critical to EndMT, endocardial cushion cell proliferation, and normal embryonic heart development.
Insights
NADPH oxidase 2 (NOX2) deficiency in mice leads to congenital heart defects by disrupting endocardial to mesenchymal transition (EndMT) and impairing endocardial cushion development. This highlights NOX2
Area of Science:
- Cardiovascular Biology
- Developmental Biology
- Molecular Cardiology
Background:
- NADPH oxidases (NOX) generate reactive oxygen species (ROS), crucial for cellular signaling in the heart.
- The specific role of NOX2 in embryonic heart development and its impact on congenital heart defects (CHDs) are not well understood.
Purpose of the Study:
- To investigate the role of NOX2 in embryonic heart development.
- To determine if NOX2 deficiency causes congenital heart defects by affecting endocardial to mesenchymal transition (EndMT).
Main Methods:
- Analysis of congenital heart defects in neonatal Nox2-deficient mice.
- Examination of embryonic heart development, focusing on endocardial cushion formation, cell proliferation, and apoptosis.
- Ex vivo studies of atrioventricular cushion explants to assess EndMT.
- Assessment of gene expression critical for heart development.
Main Results:
- 34% of Nox2-deficient neonatal mice exhibited various CHDs, including septal and valvular defects.
- Nox2 deficiency led to abnormal endocardial cushion development, characterized by reduced cell proliferation and increased apoptosis.
- Nox2 deficiency impaired ex vivo EndMT in atrioventricular cushion explants.
- Reduced expression of key developmental genes (Gata4, Tgfβ2, Bmp2, Bmp4, Snail1) was observed in Nox2-deficient hearts.
Conclusions:
- NOX2 plays a critical role in embryonic heart development.
- NOX2 is essential for regulating EndMT and endocardial cushion cell proliferation.
- NOX2 deficiency contributes to congenital heart defects through impaired EndMT and developmental gene expression.
More Related Videos
Related Concept Videos
Role Of Notch Signalling In Intestinal Stem Cell Renewal
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...
Zygotic Development And Stem Cell Formation
Mesenchymal Stem Cells
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
Notch Signaling Pathway
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...
Stem Cell Niche

