Fig. 7

Reduced Wnt/β-catenin signaling in scarb2a−/− ECs, results in abnormal CtA anastomosis and dysfunctional BBB.a–b', Optical transverse sections of Tg(kdrl:mcherry;7xTCF-Xla.Sia:GFP) in wt (a, a') and scarb2a−/− (b, b') showing reduced Wnt activity in ECs of scarb2a−/− (b, b', Nexperiments = 3, for each nwt = 3, nscarb2a−/−=3). c–e', Dorsal views of Tg(kdrl:TagBFP;glut1b:mCherry) depicting normalized glut1b expression (white) following treatment with LiCl (e, e', Nexperiments = 3, for each nwt = 6, nscarb2a−/−=6). f–h LiCl treatment significantly reduces leakage of 2000KDa Rhodamine from scarb2a−/− hindbrain vessels (h, Nexperiments = 3, for each nwt = 4, nscarb2a−/−=4). i–k Confocal images of Tg(kdrl:TagBFP) showing complete restoration of the brain vascular network after administration of LiCL and SU5416 to scarb2a mutants (k, Nexperiments = 3, for each nwt = 4, nscarb2a−/−=4). l Graphical model depicting the series of events affecting NVU formation and function in scarb2a mutant embryos. Defective endolysosomal acidification hinders Notch3 processing in RGCs, leading to imbalanced neurogenesis vs. gliogenesis, altered levels of Vegf and Wnt activation, which in turn result in defective cerebral angiogenesis, micro-hemorrhages, and compromised BBB. Scale bars a–b' = 30 μm; c–k = 60 μm.