Fig. 4. Tcf4^-/-; Lef1^-/- mutant mice have disrupted midfacial development and malformed teeth and tastebuds. (A-D) Whole-mount view of E17.0 embryos with varying dosages of Tcf4 and Lef1. (A) Tcf4 heterozygote embryos (Tcf4^+/-/Lef1^+/+) are unaffected, and epithelial specializations such as whiskers are present (black arrows), and eyelid fusion occurs normally (yellow arrow). (B) Tcf4^+/+; Lef1^-/- mutants have disrupted whisker pattern (asterisk) and exhibit hypoplastic maxillae. (C) Tcf4^-/-; Lef1^+/- mutants lack eyelids (yellow arrow). (D) Tcf4^-/-; Lef1^-/- embryos show evidence of a severely reduced maxillae, in addition to their lack of eyelids and disrupted whisker primordia (yellow arrow and black asterisk). (E-H) In a comparison of E16.0 wild type and Tcf4^-/-; Lef1^-/- compound mutants, wild-type embryos (E,F) show fully developed maxillae, an infranasal depression (dotted white line), and correctly spaced nostrils (dotted red line). Note organized whisker primordia. By contrast, Tcf4^-/-; Lef1^-/- embryos (G,H) have a malformed frontonasal prominence and underdeveloped maxillae, which results in an infranasal depression that looks more like a human philtrum (dotted white line, red arrows). The nostrils are displaced laterally as a consequence (dotted red line). Note disorganized whisker primordia and absence of fused eyelids. (I-L) In a comparison of E15.0 wild-type and Tcf4^-/-; Lef1^-/- embryos, wild-type embryos (l,J) show fully developed maxillae and organized whisker primordia; the infranasal depression (white dotted line, ind) is evident. Tcf4^-/-; Lef1^-/- embryos (K,L) exhibit hypoplastic maxillae and lack the infranasal depression (dotted white line); note the absence of whisker primordia. Scale bar: 1 mm.