Extended Data Fig. 5: β1 integrin acts upstream of perfusion-dependent activation of VEGFR3, which is required for liver growth and survival.

a, b, VEGFR3 tyrosine phosphorylation, normalized to total VEGFR3 protein, in liver lysates from E12.5 embryos with heterozygous depletion of endothelial β1 integrin (control) (a) and E12.5 endothelial β1 integrin-null embryos (b) in gain-of-perfusion experiments. n = 5 control embryos treated with control solution versus n = 9 control embryos treated with epinephrine and atropine (*P = 0.0072 (66.37;323.00)), and n = 7 control embryos treated with control solution versus n = 7 epinephrine- and atropine-treated endothelial β1 integrin-null embryos, (P = 0.3853 (−97.93; 40.64)). c, c′, d, d′, Abdominal region of an E13.5 control littermate (c′) and an E13.5 Vegfr3^−/− mouse embryo (d′). e, Calculated liver volumes (n = 5 control embryos versus n = 4 Vegfr3^−/− embryos, *P = 0.0462 (0.05; 3.86). f, f′, g, g′, Transversal sections through E13.5 livers with magnifications (f′, g′). h, Quantification of cleaved caspase-3-positive areas: n = 5 control livers versus n = 4 Vegfr3^−/− livers (*P = 0.0103 (156.50; 591.60)). i, HGF protein concentrations in lysates from embryonic livers normalized to total protein: n = 7 control embryos versus n = 10 Vegfr3^−/− embryos (*P = 0.0022 (15.55; 54.81)). Scale bars, 500 μm (c, d, f, g), 1 mm (c′, d′) and 50 μm (f′, g′). Data are mean ± s.e.m. Two-tailed unpaired Student’s t-tests, 95% confidence interval (lower confidence limit; upper confidence limit).

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