Structural studies of brain microvasculature in E10.5 embryos. Transverse sections of nonhemorrhagic brains from survivin^lox/lox (+/+) and tie1-cre/survivin^lox/lox (−/−) E10.5 embryos were cut at the level of the midbrain and stained with pericyte-specific NG-2 antibodies (A,D) and endothelial-specific CD31 antibodies (B,E), and the confocal images were overlaid (C,F). There was less intense CD31 staining in −/− embryos, with evidence of a gap between the endothelial and pericyte layers (F) compared with the +/+ (C) embryos. Transmission EM was used to examine brain microvessels (G-M) and yolk sac vessels (N-O) of survivin^lox/lox (+/+) and tie1-cre/survivin^lox/lox embryos. The endothelial cells (e) lining blood-filled (b) vessel lumens (lum) in +/+ embryos were smooth, continuous, and without gaps; contained normal mitochondria (arrow in panel H); and were immediately adjacent to surrounding pericytes (per) (I). In contrast, endothelial cell surfaces of −/− embryos were discontinous (arrows in panel J), with luminal and abluminal vesicles (arrow in panel M) and fragments of endothelial cells extending into the lumen (M), with strikingly abnormal and swollen mitochondria (arrow in panel K), and a wide space(s) between pericytes and endothelial cell layers (L). Compared with yolk sac vessels from +/+ embryos (N), yolk sac vessels from −/− embryos (O) were comprised of endothelial cells with attentuated plasma membranes, dilated endoplasmic reticulum (arrow in panel O), and nuclear chromatin condensation (double-stemmed arrow in panel O). Scale bar indicates 5 μm for panels G, J, I, and L; 2.5 μm for panel M; and 1 μm for panels H, K, N, O.