Loss of TDP-43 leads to increased vascular sprouting and defective migration. (A) More and ectopic SA sprouts in zebrafish tardbp−/−; tardbpl−/− mutants. Immunofluorescence of a sibling and a tardbp−/−; tardbpl−/− mutant embryo at 24 hpf. The Tg (fli1a:EGFP)y1 highlights the vasculature in green, the somite boundaries are stained in red. Scale bar 50 μm, anterior to the left. The insets a and b highlight the vasculature only. DA = dorsal aorta (B) Impaired directed migration in tardbp−/−; tardbpl−/− mutants. Less mutant EC nuclei have reached the DLAV at 32 hpf. Embryos are transgenic for Tg (fli1:nlsEGFP)y7 with nuclear EGFP expression (green) and Tg (kdrl:HsHRAS-mCherry)s896, highlighting the vasculature (red). Scale bar 50 μm, anterior to the left. The insets a and b highlight the EC nuclei (left) and the vasculature (right). (C) Quantifications of the vascular defects in the tardbp−/−; tardbpl−/− mutants as indicated. Kruskal–Wallis test and Dunn’s multiple comparison post test, n ≥ 9, sprouts between boundaries of six somites dorsal to the end of the yolk sack extension were quantified. D’Agostino-Pearson omnibus normality test and unpaired t-test, n = 10 for "% EC contributing to DLAV” and “number of EC in DLAV of 4 segments at 2.5 dpf”.
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