Cardiac development Notch signaling pathway

1 cardiac development

1.1 atrioventricular (av) canal development
1.2 ventricular development
1.3 ventricular outflow tract development

cardiac development

notch signal pathway plays crucial role in @ least 3 cardiac development processes: atrioventricular canal development, myocardial development, , cardiac outflow tract (oft) development.

atrioventricular (av) canal development





av boundary formation




notch signaling can regulate atrioventricular boundary formation between av canal , chamber myocardium.

studies have revealed both loss- , gain-of-function of notch pathway results in defects in av canal development. in addition, notch target genes hey1 , hey2 involved in restricting expression of 2 critical developmental regulator proteins, bmp2 , tbx2, av canal.








av epithelial-mesenchymal transition (emt)




notch signaling important process of av emt, required av canal maturation. after av canal boundary formation, subset of endocardial cells lining av canal activated signals emanating myocardium , interendocardial signaling pathways undergo emt. notch1 deficiency results in defective induction of emt. few migrating cells seen , these lack mesenchymal morphology. notch may regulate process activating matrix metalloproteinase2 (mmp2) expression, or inhibiting vascular endothelial (ve)-cadherin expression in av canal endocardium while suppressing vegf pathway via vegfr2. in rbpjk/cbf1-targeted mutants, heart valve development severely disrupted, presumably because of defective endocardial maturation , signaling.



ventricular development

some studies in xenopus , in mouse embryonic stem cells indicate cardiomyogenic commitment , differentiation require notch signaling inhibition. active notch signaling required in ventricular endocardium proper trabeculae development subsequent myocardial specification regulating bmp10, nrg1, , ephrinb2 expression. notch signaling sustains immature cardiomyocyte proliferation in mammals , zebrafish.


the downstream effector of notch signaling, hey2, demonstrated important in regulating ventricular development expression in interventricular septum , endocardial cells of cardiac cushions. cardiomyocyte , smooth muscle cell-specific deletion of hey2 results in impaired cardiac contractility, malformed right ventricle, , ventricular septal defects.

ventricular outflow tract development

during development of aortic arch , aortic arch arteries, notch receptors, ligands, , target genes display unique expression pattern. when notch pathway blocked, induction of vascular smooth muscle cell marker expression failed occur, suggesting notch involved in differentiation of cardiac neural crest cells vascular cells during outflow tract development.




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