XIAP inhibitor treated embryos develop HPE like phenotypes. (A and C) Frontal view of mouse embryos EP with XIAP shRNAi, and XIAP inhibitor, Diablo and pEGFP as a reference. Green area demarcates the brain vesicle. Red area indicates the nasal processes. Insets show unilateral electroporation of GFP in the forebrain. Quantification of relative size of (mean ± s.d.) of brain vesicles (Brain ve., green) and nasal processes (Nasal pro., red) from non-EP (Ct) and EP sides. (D) Diablo expression induces cell death in the ventral forebrain, but not in dorsal forebrain. (B, D) Cleaved Casp9 and AP2α staining in frontal sections of the front nasal region of EP embryos. Nuclei are stained with DAPI. (E) Frontal views of control (DMSO) and Embelin (100, 200 μm)-treated embryos. Blue brackets indicate the distance between the nasal processes. Red arrows illustrate the dorsal midline of the forebrain. (F and G) Quantification of midline length and relative size of (mean ± s.d.) of brain vesicles (Brain ve., green) and nasal processes (Nasal pro., red) from non-EP (Ct) and EP sides. (H–J) Embelin-treated embryos stimulate Casp9-positive cell death in ventral forebrain and neural crest (AP2α)-derived mesenchyme of medial nasal process, in associated with a decrease in Shh, Islet1/2 (Isl1/2) and Nkx2.1 activity in the ventral forebrain (I). Conversely, the domain of Pax6 expanded ventrally consistent with altered dorso-ventral patterning. White arrowheads demarcate the dorso-ventral border between Nkx2.1 and Pax6 expression. LNP, lateral nasal process; MNP, medial nasal process. Scale bars: 0.5 mm in (A)–(H) and (J); 0.2 mm in (I).