Defects in angiogenesis and heart development in Flk1 p/e–HIFdn transgenic embryos. Immunohistochemistry for PECAM-1 (except for panels G-H). (A-D) Sections of the head region at E10.5. (A,C) The PNV was formed in wild-type embryos (filled arrows), and vessels invaded the neuroepithelium (open arrows). (B,D) In transgenic embryos, the PNV was formed (arrows) but failed to sprout into the neural tissue. (E) Ventricles of the heart consisted of multiple layers of myocytes (filled arrows) and trabeculae lined with endothelial cells (open arrow) in wild-type embryos at E11.5. (F) HIFdn transgenic embryos had a thin myocard (filled arrows), poorly established trabeculation, and disorganized endocardium (open arrow). (G-H) Hematoxylin and eosin (H+E) staining of placentae at E10.5. Embryonic vessels were filled with primitive nucleated erythrocytes (arrows). (I-J) PECAM-1 staining revealed endothelial cells of embryonic vessels in the labyrinthine layer (arrows). The degree of vascularization was equal in wild-type and transgenic placentae. v indicates brain ventricle; de, maternal deciduas; la, labyrinthine layer; c, chorionic plate. Bars in panels B,F,H, 100 μm; panels D,J, 50 μm. Magnification in panels A, C, E, G, and I is the same as in panels B, D, F, H, and J, respectively.