Fig. 3: Vegfaa—Vegf receptor-2/Kdrl signaling drives outward arterial lumen remodeling. | Nature Communications

Fig. 3: Vegfaa—Vegf receptor-2/Kdrl signaling drives outward arterial lumen remodeling.

From: The GEF Trio controls endothelial cell size and arterial remodeling downstream of Vegf signaling in both zebrafish and cell models

Fig. 3

a–d aISV in WT (upper panels) and plgfmusc embryos (lower panels) treated with DMSO vehicle - control (a), low dose Vegf-R2 inhibitor (b), high dose Vegf-R2 inhibitor (c), or vegfaa ATG targeting morpholino (d). Red dotted box is displayed at higher magnification in panel below. e Quantification of aISV diameter at 50 hpf upon R2 inhibition. Mean ± s.e.m, one-way ANOVA, and post-hoc bonferroni, n = 18, 20, 20, 15, 20, 20 aISVs for indicated scenarios. **p = 0.0026, ***p < 0.001. f Quantification of aISV diameter at 48 hpf upon morpholino-mediated knockdown of vegfaa. Mean ± s.e.m, one-way ANOVA, and post-hoc bonferroni, n = 15, 22, 14, 28 aISVs for indicated scenarios. ***p < 0.001. g–j In vivo confocal imaging of WT (g), flt4−/− mutant, flt4mu407(h), flt4−/− mutant injected with flt1 ATG targeting morpholino (i), flt4−/− mutant injected with plgfmusc plasmid (j). k Quantification of images in g–j. Left panel, absolute aISV diameter (n = 21, 16, 42, 34 aISVs per indicated genotype). Right panel, aISV diameter change relative to WT. Mean ± s.e.m, unpaired two-sided students t-test. ns not significant, ***p ≤ 0.001. l, m In vivo confocal imaging of developing aISVs prior to the onset of aISV perfusion in WT (l) and plgfmusc embryos (m). Note: larger aISV prior to onset of flow in plgfmusc. n Quantification of images in l, m. Mean ± s.e.m, unpaired two-sided students t-test, n = 16 aISVs/group. ***p < 0.001. o–q Imaging of WT (o), WT treated with L-type calcium channel blocker nifedipine (p), and plgfmusc treated with nifedipine (q). r Quantification of images in o–q. Mean ± s.e.m, unpaired two-sided students t-test, n = 11, 20, and 15 aISVs per treatment group. ***p < 0.001. s–u Confocal cross-section to show lumen dimensions of aISV in WT (s), WT injected with tnnt2 targeting morpholino (t), and plgfmusc embryo injected with tnnt2 targeting morpholino (u). v Quantification of images in s–u. Mean ± s.e.m, unpaired two-sided students t-test, n = 20 aISVs per group. ***p < 0.001. Scale bar: 25 μm in all images. aISV intersegmental artery, MO morpholino, hpf hours post fertilization, RI remodeling index, tnnt2 cardiac muscle troponin T2.

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