Fig. 4. Anterior defects of the compound Dkk1^+/-;Wnt3^+/- mutant embryo. (A) The E9.5 Dkk1^+/-;Wnt3^+/- embryos display the four categories of phenotypes (Class I-IV) with different degrees of head and trunk defects, compared with single heterozygous (Dkk1^+/-;Wnt3^+/+ and Dkk1^+/+;Wnt3^+/-) embryo with normal head morphology and single homozygous mutants showing head truncation (Dkk1^-/-;Wnt3^+/+) or arrested development at gastrulation (Dkk1^+/+;Wnt3^-/-, broken white line marks the embryonic/extra-embryonic border of the embryo). (B) BATgal reporter is expressed ectopically in cells in the anterior region (red asterisks) of the E7.75 compound Dkk1^+/-;Wnt3^+/- mutant embryo. Analysis of marker expression reveals the loss of forebrain tissue at E8.5 (Fgf8, Hesx1 and Six3). In the Dkk1^+/-;Wnt3^+/- embryos, Fgf8 expression is reduced in the commissural plate (arrow) but not altered in the isthmus (black asterisk). Tissues anterior to the Hesx1-expressing domain are reduced (red asterisk). Six3 expression is reduced in the ventral forebrain (red asterisk). At E9.5, the expression domain of Nkx2.1, which marks the ventral forebrain is reduced but that of Pax6 for dorsal forebrain tissues is maintained. Broken line indicates the length of the forebrain, which is slightly shorter in the mutant embryo).