| First Author | Zhang J | Year | 2025 |
| Journal | Commun Biol | Volume | 8 |
| Issue | 1 | Pages | 880 |
| PubMed ID | 40481144 | Mgi Jnum | J:367783 |
| Mgi Id | MGI:8212062 | Doi | 10.1038/s42003-025-08312-4 |
| Citation | Zhang J, et al. (2025) Unraveling the SOX11-IGF2 signaling axis in early lung development: implications for lung disease. Commun Biol 8(1):880 |
| abstractText | The essential function of SOX11 in directing mammalian organogenesis is well-established. Nevertheless, the intricate signaling network it orchestrates, especially during early lung development, remains poorly understood. This study delves into the role of SOX11 in early lung development using a Sox11 knockout mouse model. Developmental analyses reveal that pulmonary malformations emerge during branching morphogenesis, characterized by defective epithelial-mesenchymal condensation and reduced intercellular spacing. By E18.5, Sox11(-/-) mice exhibit disrupted bronchial morphogenesis and impaired alveolar epithelial maturation. RNA sequencing reveals Igf2 as a downregulated gene, with pathways related to lung development displaying significant enrichment. IGF2 knockdown in MLE12 and A549 cells induces abnormalities in apoptosis, proliferation, migration, and polarity. ChIP-seq analyses in A549 and MRC5 cells further reveal that SOX11 regulates IGF2 without direct binding, suggesting a sophisticated regulatory network. Our findings establish the critical role of "SOX11-IGF2" signaling in early lung morphogenesis, offering theoretical insights into human lung developmental and cancers disorders. |