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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.
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