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. Author manuscript; available in PMC: 2009 Jan 1.
Published in final edited form as: Nat Genet. 2008 Jun 8;40(7):862–870. doi: 10.1038/ng.157

Figure 5. Increased canonical Wnt signaling in lung epithelium upon loss of Gata6 expression and rescue of these defects by re-expression of Fzd2 or decreased β-catenin expression.

Figure 5

Activated (β-catenin protein expression is increased in Gata6 Δ/Δ :SP-C/cre mutant airway epithelium (A and B, arrows). The BAT-GAL lacZ Wnt reporter mice show increased canonical Wnt activity in the lungs of Gata6 Δ/Δ :SP–C/cre mutants at both E13.5 (C-E) and E16.5 (F–H). This activity is dramatic and can be observed through the chest wall of the mutants at E13.5 (C, arrows). This increase in Wnt signaling is confined to airway epithelium (E and H, asterisks). Residual lacZ expression is observed in wild-type littermates in scattered mesenchymal or epithelial cells (D and G, arrowheads). The airway lumen of E11.5 lung buds from both wild-type and Gata6 Δ/Δ :SP-C/cre mutants was injected with either control plasmid or an expression plasmid encoding mouse Fzd2 and then electroporated as described in Materials and Methods (I). SP-C expression was used as a indication of rescue of epithelial defects in Gata6 Δ/Δ :SP-C/cre mutants. As expected, SP-C expression was observed in the airway epithelium of the wild-type explants (J). Gata6 Δ/Δ:SP-C/cre mutants lacked SP-C expression (K). Electroporation of the control vector did not result in increased SP-C expression (L) whereas the Fzd2 expression plasmid resulted in re-expression of SP-C (M). Gata6 Δ/Δ :SP-C/cre mutants were crossed into the β-catenirflox/+ background and expression of SP-C and CC10 was analyzed in wild-type (N and Q), Gata6 Δ/Δ :SP-C/cre mutants (O and R), and Gata6 Δ/Δ:β-catenirflox/+:SP-C/cre mutants (P and S). As expected, Gata6 Δ/Δ:SP-C/cre mutants have significantly decreased SP-C and CC10 expression with ectopic CC10 expression in distal airways (O and R, arrowheads). However, loss of one allele of β-catenin leads to a marked increase in SP-C and CC10 expression in Gata6 Δ/Δ:SP-C/cre mutants and a decrease in ectopic CC10 expression (P and S). Asterisks-airway epithelium.