ArticlePLoS biology2022
Wnt5a-Vangl1/2 signaling regulates the position and direction of lung branching through the cytoskeleton and focal adhesions.
Article in PLoS biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 11 citations in OpenAlex.
- Successful oocyte transport through the oviduct does not depend on the longitudinal alignment of oviduct epithelial folds.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- VANGL1 links angiogenesis-stemness programs and tumor microenvironment remodeling: a pan-cancer, multi-omics study with translational validation.Frontiers in oncology · 2026Article
- Decreased scleral Wnt5aNature communications · 2025Article
- Wnt5a and Notum influence the temporal dynamics of cartilaginous mesenchymal condensations in developing trachea.Frontiers in cell and developmental biology · 2025Article
- Mesenchymal Vangl1 and Vangl2 facilitate airway elongation and widening independently of the planar cell polarity complex.Development (Cambridge, England) · 2024Article
- mTORC1 signaling facilitates differential stem cell differentiation to shape the developing murine lung and is associated with mitochondrial capacity.Nature communications · 2022Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Lung branching morphogenesis requires reciprocal interactions between the epithelium and mesenchyme. How the lung branches are generated at a defined location and projected toward a specific direction remains a major unresolved issue. In this study, we investigated the function of Wnt signaling in lung branching in mice. We discovered that Wnt5a in both the epithelium and the mesenchyme plays an essential role in controlling the position and direction of lung branching. The Wnt5a signal is mediated by Vangl1/2 to trigger a cascade of noncanonical or planar cell polarity (PCP) signaling. In response to noncanonical Wnt signaling, lung cells undergo cytoskeletal reorganization and change focal adhesions. Perturbed focal adhesions in lung explants are associated with defective branching. Moreover, we observed changes in the shape and orientation of the epithelial sheet and the underlying mesenchymal layer in regions of defective branching in the mutant lungs. Thus, PCP signaling helps define the position and orientation of the lung branches. We propose that mechanical force induced by noncanonical Wnt signaling mediates a coordinated alteration in the shape and orientation of a group of epithelial and mesenchymal cells. These results provide a new framework for understanding the molecular mechanisms by which a stereotypic branching pattern is generated.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.