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.

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.

Related Concept Videos

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...
2.3K
Zygotic Development And Stem Cell Formation01:10

Zygotic Development And Stem Cell Formation

The development of all multicellular organisms starts with the fusion of haploid cells called sperm and egg to form a diploid zygote. A zygote is a totipotent cell that can develop into a complete organism. The zygote undergoes cell division or cleavage to form an 8-cell mass. Until this stage, the cells are spherical, loosely attached, and remain totipotent. Totipotent cells are capable of developing both the embryonic and the extraembryonic tissues. However, as they continue to divide, they...
6.2K
Mesenchymal Stem Cells01:19

Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their...
5.3K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.5K
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...
6.1K
Stem Cell Niche01:26

Stem Cell Niche

The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...
6.0K