ArticleAmerican journal of physiology. Lung cellular and molecular physiology2016
Rac1 modulates mammalian lung branching morphogenesis in part through canonical Wnt signaling.
Article in American journal of physiology. Lung cellular and molecular physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Novel netrin-1-Unc5b-Klf4 axis balances AT2 survival in experimental bronchopulmonary dysplasia.American journal of respiratory cell and molecular biology · 2026Article
- Co-exposure to cannabinoids and nicotine increases senescence in prenatal human lung development.Pediatric research · 2026Article
- TIAM1 drives prostatic branching phenotype and is a potential therapeutic target for benign prostatic hyperplasia.JCI insight · 2025Article
- VEGF-A isoforms induce the expression of APLN in endothelial cells during human prenatal lung development.Frontiers in cell and developmental biology · 2025Article
- Opposing roles for TGFβ- and BMP-signaling during nascent alveolar differentiation in the developing human lung.NPJ Regenerative medicine · 2023Article
- FGF18 promotes human lung branching morphogenesis through regulating mesenchymal progenitor cells.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Hedgehog Signaling Pathway Orchestrates Human Lung Branching Morphogenesis.International journal of molecular sciences · 2022Article
- Rac1 promotes kidney collecting duct integrity by limiting actomyosin activity.The Journal of cell biology · 2021Article
- Evaluation of active Rac1 levels in cancer cells: A case of misleading conclusions from immunofluorescence analysis.The Journal of biological chemistry · 2020Article
- Understanding Human Lung Development through In Vitro Model Systems.BioEssays : news and reviews in molecular, cellular and developmental biology · 2020Review
- RAC1 Involves in the Radioresistance by Mediating Epithelial-Mesenchymal Transition in Lung Cancer.Frontiers in oncology · 2020Article
- Transcriptional characterisation of human lung cells identifies novel mesenchymal lineage markers.The European respiratory journal · 2020Article
- Integration of transcriptomic and proteomic data identifies biological functions in cell populations from human infant lung.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- Discordant roles for FGF ligands in lung branching morphogenesis between human and mouse.The Journal of pathology · 2019Article
- Human lung branching morphogenesis is orchestrated by the spatiotemporal distribution of ACTA2, SOX2, and SOX9.American journal of physiology. Lung cellular and molecular physiology · 2018Article
- Epithelial heparan sulfate regulates Sonic Hedgehog signaling in lung development.PLoS genetics · 2017Article
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Authors and funding
6 authors at 2 institutions in 1 country.
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Abstract
Lung branching morphogenesis relies on a number of factors, including proper epithelial cell proliferation and differentiation, cell polarity, and migration. Rac1, a small Rho GTPase, orchestrates a number of these cellular processes, including cell proliferation and differentiation, cellular alignment, and polarization. Furthermore, Rac1 modulates both noncanonical and canonical Wnt signaling, important pathways in lung branching morphogenesis. Culture of embryonic mouse lung explants in the presence of the Rac1 inhibitor (NSC23766) resulted in a dose-dependent decrease in branching. Increased cell death and BrdU uptake were notably seen in the mesenchyme, while no direct effect on the epithelium was observed. Moreover, vasculogenesis was impaired following Rac1 inhibition as shown by decreased Vegfa expression and impaired LacZ staining in Flk1-Lacz reporter mice. Rac1 inhibition decreased Fgf10 expression in conjunction with many of its associated factors. Moreover, using the reporter lines TOPGAL and Axin2-LacZ, there was an evident decrease in canonical Wnt signaling in the explants treated with the Rac1 inhibitor. Activation of canonical Wnt pathway using WNT3a or WNT7b only partially rescued the branching inhibition. Moreover, these results were validated on human explants, where Rac1 inhibition resulted in impaired branching and decreased AXIN2 and FGFR2b expression. We therefore conclude that Rac1 regulates lung branching morphogenesis, in part through canonical Wnt signaling. However, the exact mechanisms by which Rac1 interacts with canonical Wnt in human and mouse lung requires further investigation.
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