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Blood, 1 March 2004, Vol. 103, No. 5, pp. 1710-1719.
Prepublished online as a Blood First Edition Paper on October 30, 2003; DOI 10.1182/blood-2003-06-1783.


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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY

Syndecan-2 is essential for angiogenic sprouting during zebrafish development

Eleanor Chen, Spencer Hermanson, and Stephen C. Ekker

From the Arnold and Mabel Beckman Center for Transposon Research, the Department of Genetics, Cell Biology, and Development, University of Minnesota; the Molecular, Cellular, Developmental Biology, and Genetics Graduate Program, University of Minnesota; and the Combined MD/PhD training program, University of Minnesota, Minneapolis, MN.

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.


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