2012 September 1 | Shane P. Herbert and Didier Y.R. Stainier
The article reviews the molecular control of endothelial cell (EC) behavior during blood vessel morphogenesis, focusing on the coordination of cell migration, proliferation, polarity, differentiation, and cell-cell communication. Recent studies have uncovered intricate transcriptional, post-transcriptional, and post-translational mechanisms that fine-tune signaling pathways such as vascular endothelial growth factor (VEGF) and Notch to control EC behavior during angiogenesis. These mechanisms provide insights into fundamental biological processes like tissue branching, mechanotransduction, and tubulogenesis. The review highlights the hierarchical organization of ECs into leading tip cells (TCs) and trailing stalk cells (SCs) during angiogenic sprouting, and the role of VEGF and Notch signaling in TC selection and fate determination. It also discusses the involvement of axon guidance receptors and the emerging role of microRNAs and post-translational modifications in fine-tuning angiogenic responses. The authors emphasize the parallels between angiogenesis and other biological processes, such as epithelial tracheal branching in *Drosophila*, and the potential for therapeutic targeting of angiogenic pathways in diseases like ischemic disorders and cancer.The article reviews the molecular control of endothelial cell (EC) behavior during blood vessel morphogenesis, focusing on the coordination of cell migration, proliferation, polarity, differentiation, and cell-cell communication. Recent studies have uncovered intricate transcriptional, post-transcriptional, and post-translational mechanisms that fine-tune signaling pathways such as vascular endothelial growth factor (VEGF) and Notch to control EC behavior during angiogenesis. These mechanisms provide insights into fundamental biological processes like tissue branching, mechanotransduction, and tubulogenesis. The review highlights the hierarchical organization of ECs into leading tip cells (TCs) and trailing stalk cells (SCs) during angiogenic sprouting, and the role of VEGF and Notch signaling in TC selection and fate determination. It also discusses the involvement of axon guidance receptors and the emerging role of microRNAs and post-translational modifications in fine-tuning angiogenic responses. The authors emphasize the parallels between angiogenesis and other biological processes, such as epithelial tracheal branching in *Drosophila*, and the potential for therapeutic targeting of angiogenic pathways in diseases like ischemic disorders and cancer.