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Cerebral cavernous malformations associated with loss of function of Ccm1 are shown to be formed by endothelial cells undergoing endothelial-to-mesenchymal transition (EndMT) induced by TGF-β and BMP signalling; inhibition of TGF-β and BMP signalling prevents EndMT and the appearance of CCM lesions.

The alternative splicing factor Nova2 is best known for its pivotal function in the brain. Giampietro et al. reveal an important role for Nova2 in the regulation of alternative splicing of transcripts in the vascular endothelium that are crucial for the maintenance of endothelial cell polarity and vessel lumen formation in zebrafish.

Vascular endothelium possesses remarkable plasticity in response to cues from its surroundings, leading to great heterogeneity of endothelial cells in different vascular beds. Here the authors explain the molecular basis of endothelial plasticity during embryogenesis and in various diseases.

The signalling activity of cell adhesion molecules (CAMs) such as cadherins, immunoglobulin-like CAMs or integrins has been considered a direct consequence of their adhesive properties. However, in some cases CAMs can activate signalling in the absence of cell adhesion, which significantly extends their range of biological activities.

Cerebral cavernous malformation is a vascular disease characterized by capillary-venous cavernomas in the central nervous system. Here the authors show that cavernomas display benign tumor characteristics and originate from the clonal expansion of mutated endothelial progenitors which can attract surrounding wild-type cells, inducing their mesenchymal transition and leading to growth of the cavernoma.

New blood vessels sprout from existing vasculature to ensure vascularization of developing organs and tissues. A combination of computational modelling and experimental analysis shows that sprout elongation is mediated by differential adhesion dynamics among endothelial cells. The adhesiveness of an individual endothelial cell is governed by VEGF and Notch signalling.

Vascular endothelial-cadherin is a junctional protein implicated in the control of vascular permeability. Orsenigo et al.find that vascular endothelial-cadherin is phosphorylated in veins but not in arteries of mice, and that this sensitizes vessels to rapid changes in permeability in response to inflammatory mediators.

The transcription factor Sox17 is required for the development of the vasculature in vertebrates. Here Corada et al. show that Sox17 acts downstream of Wnt signalling and upstream of Notch signalling in the regulation of artery and vein differentiation in mice.

Leukocyte recruitment from blood to areas of infection is a key step in both innate and adaptive immunological responses. The predominant model has been that leukocytes transmigrate through the junctions between adjacent endothelial cells. However, leukocytes can also migrate through the endothelial cells, and new insights suggest that both caveolae and intermediate filaments are important for this.

Pericytes and vascular smooth muscle cells are crucial for functional blood vessels, but the developmental sources of these cells are incompletely understood. Here, the authors show that endocardial endothelial cells give rise to cardiac mural cells, which are controlled by Wnt signalling.

A role for Sox18 transcription factor has been suggested by lymphatic dysfunction in the human syndrome hypotrichosis-lymphedema-telangiectasia (HLT), which is caused by mutations in Sox18. This paper shows that Sox18 directly activates Prox1 transcription. Sox18-null embryos show a complete absence of Prox1-positive lymphatic endothelial cells emanating from the cardinal vein.

Mesoangioblasts are mesodermal stem cells with a therapeutic potential for treatment of muscular dystrophy due to their ability to differentiate into skeletal muscle. This study shows that the PW1/Peg3 protein is crucial for mesoangioblast myogenic and migratory potency and is a therapeutically relevant biomarker.

Vascular endothelial growth factor is implicated in blood vessel development. In zebrafish, Hayashi et al. find that blood vessel development is dependent on the suppression of vascular endothelial growth factor by the phosphatase VE-PTP, which is recruited by activation of the angiopoietin receptor Tie2.

Glycolytic regulator PFKFB3 is a key player in vessel sprouting. Here the authors develop a computational model predicting that PFKFB3 drives endothelial cell rearrangement during vessel sprouting by promoting filopodia formation and reducing intercellular adhesion, and empirically validate this prediction.

Signals through VEGF receptor 2 (VEGFR2) increase vascular permeability, promoting cancer progression. Here the authors show that a point mutation in VEGFR2 preventing its auto-phosphorylation leads to reduced metastatic spread and improved response to chemotherapy in tumor-bearing mice, without affecting tumor inflammation.

Recent studies have elucidated important roles for members of the junctional adhesion molecule (JAM) family in controlling vascular permeability and leukocyte transmigration. Christian Weber and colleagues highlight the role of JAMs as gate keepers in inflammation and vascular pathology.