Fig. 7

Mesodermal progenitor-specific deletion of Pdgfra. (a and b) Immunohistochemistry showed PDGFRα (red) is lost in the lung mesenchyme and αSMA (green) is decreased in E18.5 Pdgfra ^Dermo1 lungs. Arrows indicate gaps in αSMA in mutant lungs. “aw” indicates airway. (c) Quantitative PCR (Q-PCR) showed a decrease in mRNA for PDGF signaling target genes, indicating an overall functional repression of the signaling pathway in E18.5 Pdgfra ^Dermo1 lungs. n = 2 pairs of separate lungs, repeated once for each. (d) Q-PCR showed myofibroblast-related genes are decreased in E18.5 Pdgfra ^Dermo1 lungs. n = 2 pairs of separate lungs, repeated once. (e) Q-PCR showing only Pparγ is robustly increased among lipofibroblast-related genes in E18.5 Pdgfra ^Dermo1 lungs. n = 2 pairs of separate lungs, repeated once. (f) Schematic model for ALK5 binary switch function in mesodermal progenitor cell fate determination. TGFβ via ALK5 is a direct activator of Prrx1 (Fig. 5f) a key transcriptional regulator of the αSMA^pos cell pathway. TGFβ via ALK5 also directly stimulates Pdgfrα mRNA (Fig. 6a), which further promotes αSMA^pos cell commitment [22]. PRRX1 and PDGFRα are reciprocal activators. In the absence of Alk5, Zfp423, which is normally repressed by TGFβ (Fig. 5l) is de-repressed, leading to activation of Pparγ [28], a transcriptional activator of lipogenic cell commitment. PRRX1 and PDGFRα inhibit adipogenesis by directly repressing PPARγ [44]. Error bars show standard error of the mean. Scale bar: b = 20 μm