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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.
Submitted June 4, 2003
Accepted October 20, 2003
Syndecan-2 is essential for angiogenic sprouting during zebrafish development
Eleanor Chen, Spencer Hermanson, and Stephen C Ekker*
Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, USA
* Corresponding author; email: ekker001{at}mail.med.umn.edu.
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 the highly-conserved cytoplasmic tail is important for the vascular function of syndecan-2. We further show that 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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