| First Author | Duong T | Year | 2014 |
| Journal | Blood | Volume | 123 |
| Issue | 7 | Pages | 1102-12 |
| PubMed ID | 24269955 | Mgi Jnum | J:208714 |
| Mgi Id | MGI:5564858 | Doi | 10.1182/blood-2013-04-495432 |
| Citation | Duong T, et al. (2014) VEGFD regulates blood vascular development by modulating SOX18 activity. Blood 123(7):1102-12 |
| abstractText | Vascular endothelial growth factor-D (VEGFD) is a potent pro-lymphangiogenic molecule during tumor growth and is considered a key therapeutic target to modulate metastasis. Despite roles in pathological neo-lymphangiogenesis, the characterization of an endogenous role for VEGFD in vascular development has remained elusive. Here, we used zebrafish to assay for genetic interactions between the Vegf/Vegf-receptor pathway and SoxF transcription factors and identified a specific interaction between Vegfd and Sox18. Double knockdown zebrafish embryos for Sox18/Vegfd and Sox7/Vegfd exhibit defects in arteriovenous differentiation. Supporting this observation, we found that Sox18/Vegfd double but not single knockout mice displayed dramatic vascular development defects. We find that VEGFD-mitogen-activated protein kinase kinase-extracellular signal-regulated kinase signaling modulates SOX18-mediated transcription, functioning at least in part by enhancing nuclear concentration and transcriptional activity in vascular endothelial cells. This work suggests that VEGFD-mediated pathologies include or involve an underlying dysregulation of SOXF-mediated transcriptional networks. |
