epithelial to mesenchymal transition involved in endocardial cushion formation

Definition

Target type: biologicalprocess

A transition where a cardiac epithelial cell loses apical/basolateral polarity, severs intercellular adhesive junctions, degrades basement membrane components and becomes a migratory mesenchymal cell that will contribute to the formation of the endocardial cushion. [GOC:mtg_heart]

Epithelial-to-mesenchymal transition (EMT) plays a critical role in endocardial cushion formation, a process that gives rise to the heart valves and septa. During early heart development, the endocardium, the inner lining of the heart, undergoes a remarkable transformation. Endocardial cells, which are typically tightly connected and form a continuous epithelial layer, lose their epithelial characteristics and acquire mesenchymal properties. This transition allows these cells to migrate from the endocardium into the underlying cardiac jelly, a matrix-rich space between the endocardium and myocardium.

The EMT process in endocardial cushion formation is orchestrated by a complex interplay of signaling pathways and transcription factors. Key players include:

* **Transforming growth factor-beta (TGF-β) signaling:** This pathway is a primary driver of EMT in various contexts, including endocardial cushion formation. TGF-β ligands bind to their receptors, triggering a cascade of intracellular events that ultimately lead to the activation of downstream transcription factors, such as Snail, Slug, and Twist.
* **Bone morphogenetic protein (BMP) signaling:** BMPs also contribute to EMT during endocardial cushion formation. They activate Smad signaling, which in turn regulates the expression of genes involved in cell migration and mesenchymal differentiation.
* **Fibroblast growth factor (FGF) signaling:** FGFs are known to regulate various aspects of heart development, including EMT. FGFs can activate downstream signaling pathways that promote cell proliferation, migration, and differentiation.
* **Wnt signaling:** Wnt pathways are crucial for regulating cell fate decisions during development, including EMT. Wnt ligands activate intracellular signaling cascades that influence gene expression and cell behavior.

These signaling pathways converge on a network of transcription factors that directly control the expression of genes involved in EMT. Transcription factors such as Snail, Slug, and Twist, which are known to be upregulated during EMT, act as repressors of epithelial genes and activators of mesenchymal genes.

As a result of EMT, endocardial cells lose their epithelial markers, such as E-cadherin, and acquire mesenchymal markers, such as N-cadherin, vimentin, and α-smooth muscle actin. This transition is accompanied by changes in cell morphology and behavior. Endocardial cells become elongated and lose their tight junctions, allowing them to migrate through the cardiac jelly.

The migrating mesenchymal cells, now called cushion mesenchyme, contribute to the formation of the endocardial cushions. These cushions are essential for the development of the heart valves and septa, ensuring proper blood flow through the heart.

In summary, EMT in endocardial cushion formation is a tightly regulated process that involves the coordinated action of signaling pathways, transcription factors, and changes in gene expression. This complex interplay ultimately leads to the transformation of endocardial cells into mesenchymal cells, which are critical for the formation of the heart valves and septa.'
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Proteins (2)

Compounds (4)