Notch signaling pathway involved in regulation of secondary heart field cardioblast proliferation

Definition

Target type: biologicalprocess

The series of molecular signals initiated by binding of an extracellular ligand to a Notch receptor on the surface of the target cell contributing to the modulation of the frequency, rate or extent of cardioblast proliferation in the secondary heart field. A cardioblast is a cardiac precursor cell. It is a cell that has been committed to a cardiac fate, but will undergo more cell division rather than terminally differentiating. [GOC:mtg_heart]

The Notch signaling pathway plays a crucial role in regulating the proliferation of cardioblasts within the secondary heart field (SHF), a crucial region for heart development. The SHF contributes to the formation of the right ventricle, outflow tract, and parts of the atria. Notch signaling is a highly conserved cell-cell communication pathway that involves a transmembrane receptor called Notch. Activation of Notch signaling occurs when a ligand, expressed on the surface of a neighboring cell, binds to the Notch receptor. This binding triggers a series of proteolytic cleavages, ultimately releasing the Notch intracellular domain (NICD). NICD translocates to the nucleus and interacts with transcription factors, leading to the activation of specific target genes.

Within the SHF, Notch signaling regulates cardioblast proliferation through a complex interplay of interactions. In the early stages of SHF development, Notch signaling promotes cardioblast proliferation, ensuring an adequate pool of cells for heart formation. This proliferative effect is mediated by Notch-dependent activation of genes like Hes1 and Hey1, which act as transcriptional repressors, inhibiting cell cycle exit and promoting proliferation.

As development progresses, Notch signaling becomes more localized and acts as a fine-tuner of cardioblast proliferation, ensuring proper heart chamber formation. In the later stages, Notch signaling promotes cell fate specification and differentiation of cardioblasts within the SHF. This involves suppressing the expression of genes associated with proliferation and promoting the expression of genes involved in differentiation. This switch in Notch signaling activity is influenced by the expression levels of different Notch ligands and receptors within the SHF, leading to varying downstream signaling events and ultimately contributing to the proper development of the heart.

In summary, the Notch signaling pathway dynamically regulates cardioblast proliferation in the SHF, influencing the formation of critical heart structures through a complex interplay of cell-cell communication, transcription factor activation, and gene regulation. Disruptions in Notch signaling can lead to heart defects, highlighting its vital role in cardiac development.'
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