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Fig. 2. Holoprosencephaly phenotypes in Cripto^3loxP/null embryos. (A-C) Lateral (A) and ventral (B,C) views of wild-type and Cripto^3loxP/null embryos at 8.25 dpc, showing anterior truncation (arrow in A) and fusion of somite pairs across the midline (C). (D-G) Lateral (D,E) and coronal (F,G) views of wild-type and Cripto^3loxP/null embryos at 9.0 dpc, showing forebrain reduction (arrows in E,G) and fusion of optic vesicles. (H) Lateral view of wild-type and Cripto^3loxP/null embryos at 10.5 dpc, showing greatly reduced forebrain and midbrain (arrow) in the mutant. (I) Lateral views of 11.5 dpc wild-type and Cripto^3loxP/null embryos, with reduced telencephalon (arrow) in the mutant. (J,K) Coronal sections of 11.5 dpc wild-type (J) and Cripto^3loxP/null mutant (K) littermates, stained with hematoxylin and eosin. While the wild-type embryo has distinct telencephalic and diencephalic vesicles, the Cripto hypomorph displays a single prosencephalic vesicle (arrow); the hindbrain appears unaffected. (L-N) Transverse sections through wild-type and Cripto^3loxP/null mutant embryos at the late neural plate/early head-fold stages, stained with Nuclear Fast Red. The wild-type embryo (L) has a midline prechordal plate that is absent in the Cripto hypomorph (M,N, arrow). Scale bars: 500 µm in A,D,E,H,I; 200 µm in B,C,F,G,J,K; 50 µm in L-N. di, diencephalic vesicles; hb, hindbrain; nt, neural tube; op, optic vesicles; pp, prechordal plate; so, somite pairs; te, telencephalic vesicles.

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