Pro-angiogenic effect of ribonuclease like 1 in zebrafish embryo development

Angiogenin (ANG) is a ribonuclease with angiogenic activity in in vitro and in vivo angiogenesis assays, but little is known about its physiological functions. Recently, the zebrafish ribonuclease like 1 (Rnasel1) gene was cloned and found to be structurally and functionally similar to human ANG. Therefore, we investigated the effect of Rnasel1 on angiogenesis during zebrafish development. In Tg (fli1:EGFP)y1 embryos injected with Rnasel1 morpholino oligonucleotides (MOs), vasculogenesis was intact, but angiogenesis was markedly impaired resulting in defective intersegmental vessels (ISVs). The impaired angiogenesis could be rescued by co-injection with MO-resistant full-length Rnasel1 mRNA. On the other hand, Rnasel1 over-expression led to ectopic ISV branching from the dorsal aorta. Mechanistically, we found that Rnasel1 promotes kinase insert domain receptor like (Kdrl) gene expression at transcriptional level. Our results indicate that Rnasel1 plays an important role in angiogenesis during zebrafish development through regulating Kdrl gene expression.