ArticleThe Journal of clinical investigation2020
Atypical cadherin FAT4 orchestrates lymphatic endothelial cell polarity in response to flow.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Several Common Genetic Variations Associate With Functional or Anatomic Effects of Anti-VEGF Treatment in Conditions With Macular Edema.Investigative ophthalmology & visual science · 2025Pooled it
- Article
- Research on the role and mechanism of FAT4 in the development and progression of tumor and non-tumor diseases.Discover oncology · 2026Review
- Molecular biology of targeting lymphangiogenesis in cancer: Therapeutic strategies and future promise.Fundamental research · 2026Review
- Insights into KIF11 pathogenesis in microcephaly-lymphedema-chorioretinopathy syndrome from a lymphatic perspective.JCI insight · 2026Article
- Mechanisms and treatments of lymphedema.Frontiers in immunology · 2026Review
- Recent advances in the study of FAT family genes in lung cancer.Discover oncology · 2025Review
- Meningeal lymphatic drainage: novel insights into central nervous system disease.Signal transduction and targeted therapy · 2025Review
- Advances in etiology, pathophysiology, diagnosis, and management of lymphedema: a comprehensive review.Frontiers in medicine · 2025Review
- Interacting Fat1 and Dchs Planar Cell Polarity Proteins Supported by Fjx1 Serve as Heterodimeric Intercellular Bridges Crucial to Support Spermatogenesis.Advances in experimental medicine and biology · 2025Review
- Characteristics and advances in signaling pathways, cellular communication, cell junctions, and oxidative stress in lymphedema.Frontiers in cell and developmental biology · 2025Review
- Functional aspects of the brain lymphatic drainage system in aging and neurodegenerative diseases.Journal of biomedical research · 2024Article
- Anti-adhesive Properties of Epoxy-Treated Xenopericardium Modified with Polyvinyl Alcohol:Sovremennye tekhnologii v meditsine · 2024Article
- Molecular pathophysiology of secondary lymphedema.Frontiers in cell and developmental biology · 2024Review
- Angiogenesis-An Emerging Role in Organ Fibrosis.International journal of molecular sciences · 2023Review
- Biomechanical control of lymphatic vessel physiology and functions.Cellular & molecular immunology · 2023Review
- Fractal dimension to characterize interactions between blood and lymphatic endothelial cells.Physical biology · 2023Article
- Structure of the planar cell polarity cadherins Fat4 and Dachsous1.Nature communications · 2023Article
- Current Status of Lymphangiogenesis: Molecular Mechanism, Immune Tolerance, and Application Prospect.Cancers · 2023Review
- Promoting Lymphangiogenesis and Lymphatic Growth and Remodeling to Treat Cardiovascular and Metabolic Diseases.Arteriosclerosis, thrombosis, and vascular biology · 2023Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The atypical cadherin FAT4 has established roles in the regulation of planar cell polarity and Hippo pathway signaling that are cell context dependent. The recent identification of FAT4 mutations in Hennekam syndrome, features of which include lymphedema, lymphangiectasia, and mental retardation, uncovered an important role for FAT4 in the lymphatic vasculature. Hennekam syndrome is also caused by mutations in collagen and calcium binding EGF domains 1 (CCBE1) and ADAM metallopeptidase with thrombospondin type 1 motif 3 (ADAMTS3), encoding a matrix protein and protease, respectively, that regulate activity of the key prolymphangiogenic VEGF-C/VEGFR3 signaling axis by facilitating the proteolytic cleavage and activation of VEGF-C. The fact that FAT4, CCBE1, and ADAMTS3 mutations underlie Hennekam syndrome suggested that all 3 genes might function in a common pathway. We identified FAT4 as a target gene of GATA-binding protein 2 (GATA2), a key transcriptional regulator of lymphatic vascular development and, in particular, lymphatic vessel valve development. Here, we demonstrate that FAT4 functions in a lymphatic endothelial cell-autonomous manner to control cell polarity in response to flow and is required for lymphatic vessel morphogenesis throughout development. Our data reveal a crucial role for FAT4 in lymphangiogenesis and shed light on the mechanistic basis by which FAT4 mutations underlie a human lymphedema syndrome.
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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.