Molecular Distinction and Angiogenic Interaction between Embryonic Arteries and Veins Revealed by ephrin-B2 and Its Receptor Eph-B4

Abstract

The vertebrate circulatory system is composed of arteries and veins. The functional and pathological differences between these vessels have been assumed to reflect physiological differences such as oxygenation and blood pressure. Here we show that ephrin-B2, an Eph family transmembrane ligand, marks arterial but not venous endothelial cells from the onset of angiogenesis. Conversely, Eph-B4, a receptor for ephrin-B2, marks veins but not arteries. ephrin-B2 knockout mice display defects in angiogenesis by both arteries and veins in the capillary networks of the head and yolk sac as well as in myocardial trabeculation. These results provide evidence that differences between arteries and veins are in part genetically determined and suggest that reciprocal signaling between these two types of vessels is crucial for morphogenesis of the capillary beds.

Cell–cell signaling via Eph receptors and ephrins

“…EphB4, EphB2 and EphB3 and their ephrin-B2 and ephrin-B1 ligands were also shown to direct the formation of the circulatory system [12]. Most significantly, Ephrin-B2 is expressed in arteries, whereas its receptor, EphB4 -in veins, thus defining their boundaries during development [13]. In addition, EphB2 and ephrin-B2 mediate the interactions between the vessel endothelial cells and the adjacent mesenchymal cells [13,14].…”

“…Most significantly, Ephrin-B2 is expressed in arteries, whereas its receptor, EphB4 -in veins, thus defining their boundaries during development [13]. In addition, EphB2 and ephrin-B2 mediate the interactions between the vessel endothelial cells and the adjacent mesenchymal cells [13,14]. An important new study [15] reveals that ephrin-B2 is also required for normal association between the blood-vessel endothelial cells and the supporting pericytes and vascular smooth muscle cells (mural cells).…”

Role for ephrinB2 in postnatal lung alveolar development and elastic matrix integrity

“…EphrinB2, a transmembrane protein endowed with its own signaling potential, is expressed on arterial and lymphatic endothelial cells (ECs) as well as perivascular cells, and its receptor, EphB4, is largely confined to venous and lymphatic endothelium (Wang et al, 1998;Adams et al, 1999;Gerety et al, 1999;Makinen et al, 2005) Experiments using gene targeted mice have shown that these proteins are crucial for embryonic sprouting angiogenesis, and together with other family members could contribute greatly to specialization and maturation of vascular beds (Heroult et al, 2006).…”

“…The final vascular response to ephrinB2 engagement with its receptors on adjacent cells is shaped by bidirectional signaling interactions within endothelial populations and between endothelial cells and adjacent nonendothelial populations (Heroult et al, 2006). The interaction between ephrinB2 and EphB4 within vascular endothelia may provide the critical repulsion signals required to set arterial-venous boundaries, reminiscent of their repulsive guidance of axonal growth cones (Wang et al, 1998;Adams et al, 1999;Gerety et al, 1999;Gerety and Anderson, 2002). However, ephrinB-Eph interaction can also stimulate endothelial cell sprouting (Adams et al, 1999;Palmer et al, 2002).…”

Différenciation artérioveineuse : génétique ou hémodynamique ?

“…Toutes sont également exprimées dans le système nerveux où elles contrô-lent la destinée et le guidage des précur-seurs neuronaux et des axones, ce qui suggère leur rôle dans l'établissement du réseau vasculaire. Les CE artérielles du poisson zèbre, du poulet et de la souris expriment sélectivement l'éphrine-B2, la neuropiline 1 (NRP1), le récepteur notch3, le ligand de Notch Delta-like 4 et gridlock [5][6][7][8][9][10][11][9][10][11][12][13][14][15][16]. D'autres molécules sont spécifiquement exprimées par les CE veineuses, notamment EphB4, le récepteur du marqueur artériel éphrine-B2 [12].…”