Cellular and molecular analyses of vascular tube and lumen formation in zebrafish.
Tube and lumen formation are essential steps in forming a functional vasculature. Despite their significance, our understanding of these processes remains limited, especially at the cellular and molecular levels. In this study, we analyze mechanisms of angioblast coalescence in the zebrafish embryonic midline and subsequent vascular tube formation. To facilitate these studies, we generated a transgenic line where EGFP expression is controlled by the zebrafish flk1 promoter. We find that angioblasts migrate as individual cells to form a vascular cord at the midline. This transient structure is stabilized by endothelial cell-cell junctions, and subsequently undergoes lumen formation to form a fully patent vessel. Downregulating the VEGF signaling pathway, while affecting the number of angioblasts, does not appear to affect their migratory behavior. Our studies also indicate that the endoderm, a tissue previously implicated in vascular development, provides a substratum for endothelial cell migration and is involved in regulating the timing of this process, but that it is not essential for the direction of migration. In addition, the endothelial cells in endodermless embryos form properly lumenized vessels, contrary to what has been previously reported in Xenopus and avian embryos. These studies provide the tools and a cellular framework for the investigation of mutations affecting vasculogenesis in zebrafish.
Jin
Suk-Won
SW
Department of Biochemistry and Biophysics and Cardiovascular Research Institute, Program in Developmental Biology, University of California San Francisco, 1550 Fourth street, San Francisco, CA 94143, USA.
Beis
Dimitris
D
Mitchell
Tracy
T
Chen
Jau-Nian
JN
Stainier
Didier Y R
DY
D000818:Animals; D030801:Animals, Genetically Modified; D001808:Blood Vessels / Q000166:cytology* / Q000196:embryology / Q000254:growth & development*; D019521:Body Patterning; D002465:Cell Movement; D004625:Embryo, Nonmammalian; D004707:Endoderm / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology; D049452:Green Fluorescent Proteins / Q000235:genetics; D007365:Intercellular Junctions / Q000502:physiology; D011401:Promoter Regions, Genetic; D013234:Stem Cells / Q000166:cytology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics; D015027:Zebrafish
D049452:Green Fluorescent Proteins; D040301:Vascular Endothelial Growth Factor Receptor-2