Fig. 4: Depleting VOGM candidate genes in zebrafish lead to aneurysm-like phenotypes.

a Schematic showing layout of cranial arteries (red) and veins (blue) in 48 hpf zebrafish wt and mutant embryos. We attempted to identify phenotypes in any of the following vessels: primordial hindbrain channel (PHBC), basilar artery (BA), posterior communicating segment (PCS), and dorsal aorta (DA). Also pictured: duct of Cuvier (DoC). Generally, we observed enlarged PHBC and PCS vessels. b Cranial vasculature indicated by Tg(kdr:gfp) and dextran microangiography of 48 hpf wt and ephb4a/b-depleted zebrafish embryo. Scale bar: 100 µm. Cranial vasculature is indicated by Tg(kdr:gfp), dextran microangiogram, and merged channels of the wt and ephb4a/b-deleted embryo. Ventrally restricted confocal substacks emphasizing PCS (dashed lines) are shown. Ventrally restricted confocal substack which emphasizing PCS (dashed lines) shows enlarged PCS in ephb4a/b-depleted zebrafish. Altogether, 46 independent larvae were imaged from 15 independent experiments. c Cranial vasculature indicated by Tg(kdr:gfp) and dextran microangiography of 48 hpf embryos following acvrl1 gRNA targeting, rescue, and false rescue with C344Y variant. Scale bar: 150 µm. Cranial vasculature is indicated by Tg(kdr:gfp) and dextran microangiogram (merged). Ventrally restricted confocal substacks emphasizing PCS (lower row) are shown. This confocal substack shows enlarged PCS in targeted embryos which can be rescued with wt mRNA but not C344Y mRNA. Note that PHBC is also enlarged in targeted embryos. d Quantification of PCS results (two-sided Wilcoxon signed-rank test, not adjusted). we also injected scrambled acvrl1 gRNA as a further negative control. *** ≤ 0.001, ** ≤ 0.01, * ≤  0.05. n = 66 independent larvae taken from 14 independent experiments. Error bars are ± standard error of the mean.