Fig. 2 | Nature Communications

Fig. 2

From: High mitogenic stimulation arrests angiogenesis

Fig. 2

Dll4/Notch signalling inhibition induces context-dependent proliferative effects. ad Confocal micrographs of the postnatal retinal vasculature from animals treated at P5 with IgG (control) or anti-Dll4 for 24 h (a, b) or 48 h (c, d). Anti-Erg (red) labels EC nuclei. EdU labels the nuclei of all cells in S-phase in the previous 4 h. Blue nuclei mark non-endothelial cells in S-phase, and double-positive (Erg+/EdU+) cell nuclei are pseudocoloured green to better highlight ECs in S-phase. Scale bars, 200 μm. eh Comparison of indicated parameters in large microscopic fields of antibody treated retinas (n = 4 mice per group). Inhibition of Dll4/Notch signalling with anti-Dll4 leads to fast (24 and 48 h) endothelial expansion (number of Erg+ cells per field) followed by premature cell-cycle exit at the angiogenic front (e, f) and cell-cycle re-entry by mature ECs (gh), which are indicated by the changes observed in the frequency of Erg+ cells in S-phase (EdU+). i, j EC-specific deletion of the Dll4 gene from P4 to P7, results in a similar proliferative response. Scale bars, 70 μm. k Comparison of indicated parameters in large microscopic fields of control (n = 3) and mutant (n = 3) mice retinas. Error bars indicate std. dev.; NS nonsignificant; ***p < 0.0005. One-way ANOVA with Tukey’s post hoc test (eh) or two-tailed unpaired t test (k). Source data are provided as a Source Data file

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