Syndecan-2 is essential for angiogenic sprouting during zebrafish development.
We used a morpholino-based gene-targeting screen to identify a novel protein essential for vascular development using the zebrafish, Danio rerio. We show that syndecan-2, a cell-surface heparan sulfate proteoglycan, is essential for angiogenic sprouting during embryogenesis. The vascular function of syndecan-2 is likely conserved, as zebrafish and mouse syndecan-2 show similar expression patterns around major trunk vessels, and human syndecan-2 can restore angiogenic sprouting in syndecan-2 morphants. In contrast, forced expression of a truncated form of syndecan-2 results in embryos with defects in angiogenesis, indicating that the highly conserved cytoplasmic tail is important for the vascular function of syndecan-2. We further show that vascular endothelial growth factor (VEGF) and syndecan-2 genetically interact in vivo using both gain-of-function and loss-of-function studies in zebrafish. VEGF-mediated ectopic signaling is compromised in syndecan-2 morphants, and ectopic syndecan-2 potentiates ectopic VEGF signaling. Syndecan-2 as a novel angiogenic factor is a potential candidate for use in the development of angiogenesis-based therapies.
Chen
Eleanor
E
Arnold and Mabel Beckman Center for Transposon Research, Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA.
Hermanson
Spencer
S
Ekker
Stephen C
SC
D020121:5' Untranslated Regions; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins; D019812:Heparan Sulfate Proteoglycans / Q000737:chemistry; D006801:Humans; D017403:In Situ Hybridization; D008164:Luminescent Proteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic; D010641:Phenotype; D010802:Phylogeny; D011485:Protein Binding; D011509:Proteoglycans / Q000096:biosynthesis* / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D053669:Syndecan-2; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins
D020121:5' Untranslated Regions; D019812:Heparan Sulfate Proteoglycans; D008164:Luminescent Proteins; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D012333:RNA, Messenger; C508245:SDC2 protein, human; C508246:Sdc2 protein, mouse; D042461:Vascular Endothelial Growth Factor A; D029961:Zebrafish Proteins; C508249:sdc2 protein, zebrafish; D049452:Green Fluorescent Proteins; D053669:Syndecan-2