Fig. 2. Severe placental defects in c-myc^ORF/ORF embryos. (A) Immunohistochemical analysis of c-Myc expression in the E10.5 wild-type placenta. c-Myc expression is detected in the embryonic parts of the placenta, including the chorionic plate (CP), labyrinth layer (La), spongiotrophoblast (Sp), trophoblast giant cells (TGC) and in hematopoietic cells derived from the embryo, which are located in the fetal blood spaces (inset A'). (B-D) Comparison of control (left) and c-Myc null (c-myc^ORF/ORF) embryos (right) at E10.5. (B) Hematoxylin and eosin (H&E) staining of control and c-Myc-deficient placenta at E10.5. The bottom panels show an enlargement of the boxed areas in the top panels. (C) Analysis of placental vascularization. Laminin (pink) is expressed on embryonic vessels and defines fetal blood spaces. Cytokeratin (brown) marks trophoblast cells and defines maternal blood spaces. The bottom panels show an enlargement of the boxed areas in the top panels. The white line demarcates the failure of vessels (pink) to invade into the trophoblast (brown) layer (D) Bromodeoxyuridine (BrdU) incorporation analysis of E9.5 control and c-Myc-deficient placenta. Highly proliferating (BrdU+; arrows) tissues are present in control (left) but not in c-myc^ORF/ORF (right) placentas. (E) Hematoxylin and eosin (H&E) staining of control and Sox2Cre;c-myc^flox/flox placenta at E10.5. Placental developmental defects are rescued with respect to c-myc^ORF/ORF in B.