Figure 7

Hmga2 acts upstream of Gata6 in WNT signaling regulation. (A) Gata6 and Fzd2 are required for the effect of Hmga2 GOF on expression of WNT targets. Expression analysis of the indicated genes by quantitative RT-PCR in MLE-12 cells that were transfected with either control (Ctrl) or Gata6- or Fzd2-specific siRNA and Hmga2 expression plasmid as indicated. Data are presented as mean ± SEM (n = 4). ***P <0.001; **P <0.01; *P <0.05 after one-way analysis of variance. (B) Gata6-GOF rescued the effect of Hmga2-LOF on expression of WNT targets. Expression analysis of the indicated genes by quantitative RT-PCR in MLE-12 cells that were transfected with either control (Ctrl) or Hmga2- or Fzd2-specific siRNA and Gata6 expression plasmid as indicated. Data are presented as mean ± SEM (n = 4) and asterisks as in A. (C) Model. Hmga2 regulates WNT signaling at different points of the pathway. Regulation of the secreted WNT glycoproteins (Wnt2b, Wnt7b and Wnt11) mediates the paracrine effect on the mesenchyme of the embryonic lung. In addition, HMGA2-mediated regulation of Gata6 is a key process in fine-tuning the activity of canonical WNT signaling in developing airway epithelium. X, unknown transcription factor.