Fig. 6. Synergistic requirement for Smad2 and Smad3 in the patterning and organization of the early post-implantation embryo. Whole-mount views or transverse sections of embryos within the deciduum of E7.5 (A,E,I,M,Q) wild-type (WT; anterior towards the left), (B,F,J,N,R) Smad2^–/–, (C,G,K,O,S) Smad2^–/–;Smad3^+/– and (D,H,L,P,T) Smad2^–/–;Smad3^–/– embryos hybridized with (I-L) Oct4, (M-P) Bmp4 or (Q-T) Sox2 riboprobes. (A,E) Wild-type embryos have distinct embryonic and extra-embryonic regions (separated by broken line), with embryonic (m) (E) and Bmp4-expressing extra-embryonic (xm) mesoderm formation (E,M), and Oct4-expressing epiblast (ep) (I). (M) Bmp4 and (Q) Sox2 transcripts identify the extra-embryonic ectoderm (xc) (E) and its derivative the chorion (ch). Smad2^–/– embryos express little Oct4 (J) and form exclusively Bmp4-positive extra-embryonic mesoderm (F,N), which displaces the extra-embryonic ectoderm normally to form the chorion (ch) (F,J,N,R). Smad2^–/–;Smad3^+/– mutant embryos undergo cavitation, but show no clear embryonic/extra-embryonic boundary, and are enveloped by a prominently folded and thickened layer of visceral endoderm (C,G,K,O,S) that surrounds disorganized extra-embryonic ectoderm (G,O,S), with little to no formation of presumptive extra-embryonic mesoderm (xm*) (G). (D,L,P,T) Smad2^–/–;Smad3^–/– embryos develop as a small disorganized tissue mass within the parietal yolk sac endoderm (pe). Sections reveal rudimentary epithelial development with no mesoderm formation (H). Double mutants lack Oct4 (L), but consistently show expression of Bmp4 (P) and Sox2 (T), suggesting loss of embryonic ectoderm and unique formation of extra-embryonic ectoderm (xc*) (H). ae, anterior ectoderm.