Fig. 4. BMP signalling is required in the epiblast for mesoderm specification and to inhibit neural differentiation. (A,B) At 5.5 dpc, pSmad1/5/8 expression is slightly decreased in the epiblast of Bmpr1a^-/fx; Sox2Cre^+/- mouse embryos (n=4/7) as compared with controls. (C,D) At 6.5 dpc, in Bmpr1a^-/fx; Sox2Cre^+/- embryos pSmad1/5/8 expression is severely reduced in the epiblast (n=4/7) and (E,F) by 7.5 dpc is almost lost (n=4/4), although some expression in the visceral endoderm remains at both these stages. (A'-F') Overlay of pSmad1/5/8 and nuclear staining. (G,H) At 6.5 dpc, Fgf8 is expressed in the posterior epiblast of controls but its expression is reduced or lost in the majority of Bmpr1a^-/fx; Sox2Cre^+/- embryos (n=4/6). (I,J) Cripto is expressed in the posterior epiblast of controls at 6.5 dpc but is lost in a proportion of Bmpr1a^-/fx; Sox2Cre^+/- embryos (n=3/9). (K,L) At 6.5 dpc, Nodal is expressed in the posterior epiblast of controls, but when Bmpr1a is deleted from the epiblast Nodal expression is reduced or lost (n=3/4). (M,N) At 7.25 dpc, Hesx1 is expressed in the anterior definitive endoderm and anterior neural ectoderm of controls. A large expansion in the domain of Hesx1 expression is observed in the epiblast of Bmpr1a^-/fx; Sox2Cre^+/- embryos (n=4/6). (O,P) Six3 is a marker of the anterior neural ectoderm at 7.5 dpc. In Bmpr1a^-/fx; Sox2Cre^+/- embryos, Six3 expression is greatly expanded (n=7/8). (Q,R) At 7.5 dpc, Sox1 is not expressed in control embryos but can be found throughout the epiblast of Bmpr1a^-/fx; Sox2Cre^+/- embryos. All are lateral views, anterior to the left.