Fig. 7. Circulating RA rescues Raldh2^-/- vascular defects. Pregnant Raldh2^+/- females were fed chow containing 0.1 mg/g all-trans RA from E7.5-8.5, E7.5-9.5 or E7.5-12.5, killed at E12.5 and examined histologically. Mutants were compared with wild-type embryos from mothers fed RA from E7.5-12.5 (first column), which were no different from wild-type embryos from chow-fed mothers. In mutants exposed to RA from E7.5-8.5 (second column), yolk sacs exhibited formation of some large vessels (arrowheads), but all smaller caliber vessels (arrows) were significantly dilated. Exposure to RA from E7.5-9.5 (third column) induced formation of a larger number of branched vessels (arrowheads), but dilation of small vessels (arrows) was still evident. Exposure to RA from E7.5-12.5 (fourth column), lead to vascularization of mutant yolk sac equivalent to wild type; large (arrowheads) and small (arrows) vessels were similar in caliber and distribution. The mitotic index of yolk sac tissue (bottom row) from `rescued' mutants was evaluated via immunostaining for phosphohistone 3 and significantly elevated for all, compared with wild type, except those exposed to RA at E7.5-12.5.