TBX4 coordinates multiscale regulatory networks in lung development. (IMAGE)
Caption
This figure illustrates that TBX4 is pivotal in lung branching morphogenesis, with its expression spanning various cell types, including fibroblasts, perivascular cells, and airway smooth muscle cells, across different lung development stages. Sox9/Nkx2-1 epithelial progenitor cells secrete Shh, which activates Gli2/3 in mesenchymal cells and induces Foxf1 expression. Foxf1 synergizes with TBX4 to activate Wnt2/2B and FGF10, crucial for lung duct formation and growth. Mesenchymal FGF10 activates Fgfr2 in Sox9/Nkx2-1 epithelial progenitor cells, boosting VEGFA production for lung vascularization. The FGF10-Shh feedback loop, mediated by ETV4/5, ensures orderly lung branching. RNA-binding protein HuR may stabilize FGF10 and TBX4 mRNA, while BMP-Smad signaling modulates Tbx4 expression/function, activating P-Smad1/5 to enhance fibroblast invasiveness. TBX4 also regulates the extracellular matrix by activating Has2, increasing HA to support lung development. These interconnected regulatory mechanisms ensure proper lung branching morphogenesis
Credit
Lin Yi, Li Zhou, Bianfei Shao, Tingxiu Xiang, Jingyi Tang
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CC BY-NC-ND