Unraveling the SOX11-IGF2 signaling axis in early lung development: implications for lung disease
Abstract 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 us...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-06-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08312-4 |
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| Summary: | Abstract 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. |
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| ISSN: | 2399-3642 |