Diversity Is in My Veins Role of Bone Morphogenetic Protein Signaling During Venous Morphogenesis in Zebrafish Illustrates the Heterogeneity Within Endothelial Cells

Endothelial cells are a highly diverse group of cells which display distinct cellular responses to exogenous stimuli. Although the aptly named vascular endothelial growth factor-A signaling pathway is hailed as the most important signaling input for endothelial cells, additional factors also participate in regulating diverse aspects of endothelial behaviors and functions. Given this heterogeneity, these additional factors seem to play a critical role in creating a custom-tailored environment to regulate behaviors and functions of distinct subgroups of endothelial cells. For instance, molecular cues that modulate morphogenesis of arterial vascular beds can be distinct from those that govern morphogenesis of venous vascular beds. Recently, we have found that bone morphogenetic protein signaling selectively promotes angiogenesis from venous vascular beds without eliciting similar responses from arterial vascular beds in zebrafish, indicating that bone morphogenetic protein signaling functions as a context-dependent regulator during vascular morphogenesis. In this review, we will provide an overview of the molecular mechanisms that underlie proangiogenic effects of bone morphogenetic protein signaling on venous vascular beds in the context of endothelial heterogeneity and suggest a more comprehensive picture of the molecular mechanisms of vascular morphogenesis during development.