Fig. 7 | Nature Communications

Fig. 7

From: High mitogenic stimulation arrests angiogenesis

Fig. 7

p21 inhibits proliferation of ECs exposed to high-mitogenic stimulation. ad ECs (ERG+ nuclei) in control and p21 knockout retinas (a) have similar frequencies of cells in S-phase (Erg+/EdU+ double-positive cells, pseudocoloured green). After administration of anti-Dll4 antibody for 48 h (b), the frequency of S-phase ECs decreased significantly in control retinas due to cell-cycle arrest. In p21 knockout retinas, anti-Dll4-induced cell-cycle arrest was less frequent (c), and resulting in the generation of more ECs (d). Charts show quantification of large microscopic fields from several control and mutant retinas (IgG 48 h, n = 4; p21KO IgG 48 h, n = 4; a-Dll4 48 h, n = 5; p21KO a-Dll4 48 h, n = 6). e, f Confocal micrographs of retinas from P6 Esm1-HA-H2B-Cerulean-2A-iCreERT2 mice (n = 4) and corresponding chart (f), showing that 70% of Esm1+ tip-ECs (HA+, red) are p21+ (green), as indicated by the yellow arrowheads. g, h Confocal micrographs of P6 retinas from control (n = 4) and p21KO (n = 4) mice carrying the Esm1-HA-H2B-Cerulean-2A-iCreERT2 allele, showing that p21 blocks tip-EC proliferation (yellow arrowheads indicate Ki67+, Esm1+ tip-ECs) but does not affect stalk-EC proliferation. Scale bars in all panels, 50 μm. Error bars represent SEM (c, d) or std. dev. (f, h). NS nonsignificant; *p < 0,05; **p < 0.005. One-way ANOVA with Tukey’s post hoc test (c, d), two-tailed unpaired t test (f, h). Source data are provided as a Source Data file

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