VEGFA triggers vessel regression in

VEGFA triggers vessel regression in cds2-deficient zebrafish embryosWe previously reported that zebrafish cds2 mutants carried endothelium-specific morphogenic defects with impaired angiogenesis of intersegmental vessel (ISV) and reduced VEGFA signal activity28. During the phenotype scoring on zebrafish cds2 mutants (Fig. 1a, b), we found there were always about 5–10% embryos showing more severe, while about 15–20% showing less severe vascular defects, compared to the majority of cds2 mutants (Fig. 1b). After checking the expression level of vegfaa (the major vegfa isoform in zebrafish embryos that governs vasculogenesis and angiogenesis)29,30,31, we found these cds2 mutants with severe vascular defects expressed a higher level of vegfaa, compared to those with a weaker phenotype (Fig. 1c), which is opposite to our expectation. We further analyzed Hif1a pathway and found that Hif1a protein was accumulated and its downstream signaling was activated in cds2 mutants with severe defective vessel phenotype (Supplementary information, Fig. S1a, b), indicating hypoxia might cause upregulation of vegfaa.