Vascular abnormalities in <i>Ccn2</i> mutant embryos.

<p>(A) E18.5 WT and (B) <i>Ccn2−/−</i> littermate, showing vessel dilation throughout the mutant embryo. (C, D) H&E-stained paraffin sections through the lumbar dorsal dermis of (C) E18.5 WT and (D) <i>Ccn2−/−</i> littermate. Arrowheads point to vessels. Bars highlight the enlarged distance between the hypodermal and epidermal layers in the mutant, indicative of local edema. (E,F) Hematoxylin and eosin-stained sections through E16.5 WT (E) and <i>Ccn2−/−</i> (F) descending aorta at thoracic level. Smooth muscle cells in the tunica media are spindle-shaped and arranged in layers in the WT embryo, but are more cuboidal and disorganized in the <i>Ccn2−/−</i> littermate. (G,H) Higher magnification images through aorta at lumbar level in E16.5 (G) WT and (H) <i>Ccn2−/−</i> littermate showing spindle-shaped smooth muscle cells (arrowheads) in WT that have a cuboidal shape in the mutant. (I,J) Confocal images of PECAM-stained dorsal dermal vasculature in (I) WT and (J) <i>Ccn2−/−</i> littermates. Arrows demarcate arterial elements; arrowheads demarcate venous elements; asterisks identify capillary beds. (K,L) Higher magnification confocal images of (K) WT and (L) <i>Ccn2−/−</i> dorsal dermal capillary beds, showing increased capillary density in the mutant. (M,N) High magnification confocal image of (M) WT and (N) <i>Ccn2−/−</i> dorsal dermal capillaries, showing numerous abluminal protrusions (arrows in (N)) on the mutant capillary. (O,P) Electron micrographs of newborn (P0) (O) WT and (P) <i>Ccn2−/−</i> dermal capillaries, showing abluminal and luminal (arrows in (P)) protrusions.