Endothelial-Myocardial Angiocrine Signaling in Heart Development

Figures

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  FIGURE 1. Role of angiocrine signaling in cardiac chamber ballooning, trabeculation, and compaction during cardiac development. Angiocrine signaling of cardiac endothelial cells governs major cellular and molecular processes in mammalian heart development. (A) Ballooning is achieved by more active proliferation in the outer curvature (OC) than in the inner curvature (IC), and this asymmetric proliferation between the inner and outer curvatures is associated with Klf2 and cilia signaling in endocardial cells activated by wall shear stress (WSS). (B) Initiation of trabeculation and growth of trabeculae (orange) in ECM bubble are regulated by Nrg1 secreted by endocardial cells (red). After trabeculation, compaction requires angiocrine signaling in both coronary endothelial cells (green) and endocardial cells (red). Endothelial dysfunction can cause left ventricular noncompaction (LVNC). Trabecular and compact cardiomyocytes are indicated in orange and yellow, respectively. E10, mouse embryonic day 10; OFT, outflow tract; RV, right ventricle; LV, left ventricle; CA, common atrium; AVC, atrioventricular canal; ECM, extracellular matrix; and P3, postnatal day 3.

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  FIGURE 2. Endothelial-to-mesenchymal transition (EndoMT) of valve endothelial cells expressing JB3 and angiocrine signaling during valve formation between E9.5 and E14.5. Valve formation is initiated by EndoMT of valve endothelial cells (purple) to become valve interstitial cells (blue) in cardiac jelly. During valve formation, the cushion is remodeled and elongated by valve interstitial cells, and the mature valve leaflet is supported by chordae tendineae. Endocardial cells and cardiomyocytes are indicated in red and yellow, respectively. OFT, outflow tract; AVC, atrioventricular canal; E9.5, E11.5, E14.5, mouse embryonic day 9.5, 11.5, 14.5, respectively.