Molecular control of arterial-venous blood vessel identity

Abstract

Recent research has demonstrated that not only haemodynamic factors but also genetic programmes control arterial-venous cell fate and blood vessel identity. The identification of arteries and veins was previously based solely on morphological criteria and is now greatly facilitated by specific molecular markers. Moreover, signalling pathways controlling the arterial-venous decision during embryonic development have been outlined for the first time. This review gives an up-to-date overview of differentially expressed genes and the regulatory processes leading to the differentiation of arteries and veins.

Fig. 1

Organization of the arterial–venous network. Distinct molecular AV identity could play various roles during early vascular morphogenesis. Repulsive cues (open arrows) provided by Eph/ephrin signalling and other pathways might restrict cell movement across an AV boundary and inhibit the formation of shunts between large-calibre blood vessels. Formation of capillary beds by angiogenesis might be stimulated at the AV interface. Distinct molecular properties of arteries and veins could contribute to the recruitment of pericytes and vascular smooth muscle cells, and perhaps mediate specific interactions between endothelial cells and the adjacent mesenchyme. Haemodynamic factors are also likely to contribute to AV differentiation (arrows indicate the direction of blood flow).

Fig. 2

Arterial–venous cell fate decision in zebrafish embryos. Signalling pathways in the lateral posterior mesoderm and in the large blood vessels are shown (a). Sonic Hedgehog provided by the notochord has been recently shown to induce VEGF expression in somites and regulate the arterial identity of endothelial cells in the aorta. Neuropilin-1, which is expressed by arterial ECs in mouse, could perhaps mediate artery-specific VEGF signalling. Differences between pathways in the lateral posterior mesoderm and the main blood vessels might exist. Venous cell fate might be driven by unknown pathways or could be the default outcome in the absence of arterial signals. Blood vessels are disrupted or change their molecular AV identity in certain zebrafish mutants or in response to experimental manipulation (b,c). Note that arrows do not necessarily indicate direct interaction or regulation.