Wnt signaling in the vasculature.

The development of the vascular system requires orchestrated activities of various molecular pathways to assure the formation of a hierarchically branched tubular network. Furthermore, endothelial cell (EC) populations are heterogeneous to meet organ-specific requirements in the mature vasculature. This developmental scheme is probably best represented by the acquisition and maintenance of unique barrier properties known as the blood-brain barrier (BBB) in microvessels of the central nervous system (CNS). Only recently, the canonical Wnt/β-catenin pathway was implicated in many aspects of angiogenesis, vascular remodeling and differentiation in various species and organ systems. Beside its major contribution to brain angiogenesis and barrier formation, the Wnt/β-catenin pathway influences vascular sprouting, remodeling and arterio-venous specification by modulating the Notch pathway. Furthermore, canonical Wnt signaling has been implicated in heart valve formation by initiating endothelial-mesenchymal transition. Growing evidence also points to a role of the non-canonical Wnt pathway in vascular development by regulating VEGF availability. Several novel findings regarding the role of the Wnt pathway in developmental as well as in pathological angiogenesis prompted us to review its emerging function in the vasculature.