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Fig. 1. Vascular plexus formation and remodeling. Embryos and yolk sacs were dissected at E8.25-8.5 (three- to six-somite stage). Morphological examination revealed that a vascular plexus had formed in both wild-type (A) and Raldh2^-/- (B) yolk sac tissues. Hematoxylin and Eosin (H/E) staining of 5 µm paraffin wax-embedded sections of yolk sacs revealed dilated vessels within the Raldh2^-/- plexi (D) compared with wild type (C). Embryos and yolk sacs were also dissected at E9.5. Morphological examination of wild-type yolk sacs (E) revealed a well-defined, branched network that circulated blood throughout the embryo. Yolk sacs of Raldh2^-/- mutants (F) exhibited no remodeling and lacked large vitelline vessels. In wild-type yolk sac (G), SM- ${alpha}$ -actin expression was evident around large vessels. In Raldh2^-/- yolk sacs (H), investment of endothelial tubes by SM- ${alpha}$ -actin-positive cells was not evident.

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