Fig. 7: Vascular-specific expression of EPHB4 F867L alone during mid to late gestation results in blood and lymphatic vascular abnormalities.
From: Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations
Embryos of the indicated genotypes were administered tamoxifen (TM) at E13.5 and harvested at E17.5 or E18.5. At left are images of whole embryos (n = 3 each genotype). Note evidence of blood-filled lymphatics (BFL) in skin of E17.5 Ephb4fl/F867L Cdh5-CreERT2 embryos (arrows) but not in control littermate Ephb4fl/F867L embryos. Staining of skin sections with H&E and anti-CD31, and anti-LYVE-1 antibodies revealed dilated blood-filled lymphatics in Ephb4fl/F867L Cdh5-CreERT2 embryos. Note generalized hemorrhage in skin of E18.5 Ephb4fl/F867L Cdh5-CreERT2 embryos (arrows) but not in control littermate Ephb4fl/+ Cdh5-CreERT2 embryos, confirmed by staining of tissue sections with H&E. Staining of E18.5 tissue sections with anti-CD31 anti-LYVE-1 antibodies revealed near complete absence of lymphatic vessels in skin of E18.5 Ephb4fl/F867L Cdh5-CreERT2 embryos compared to E17.5 and E18.5 controls. Images of H&E-stained brain sections are of the cerebellar/choroid plexus region. Note evidence of hemorrhage (extravascular erythrocytes) in E17.5 Ephb4fl/F867L Cdh5-CreERT2 embryos (arrows) but not in controls. The E18.5 brain of Ephb4fl/F867L Cdh5-CreERT2 embryos shows extensive loss of cellularity and total absence of erythrocytes. CD31 staining of brain sections shows disorganized vascular structures in Ephb4fl/F867L Cdh5-CreERT2 embryos compared to controls in the region of the choroid plexus and cerebellum.
