ArticleThe Journal of clinical investigation2016
Foxc1 and Foxc2 deletion causes abnormal lymphangiogenesis and correlates with ERK hyperactivation.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 79 citations in OpenAlex.
- Lysophosphatidic acid-mediated NF-κB activation promotes FOXC2 expression essential for lymphatic valve development.The Journal of clinical investigation · 2026Article
- The role of the cardiac lymphatic system in heart failure "reverse remodeling": from developmental signals to druggable targets.Frontiers in immunology · 2026Review
- SCIG: Machine learning uncovers cell identity genes in single cells by genetic sequence codes.Nucleic acids research · 2025Article
- The immune regulatory role of lymphangiogenesis in kidney disease.Journal of translational medicine · 2024Review
- FOXC1 regulates endothelial CD98 (LAT1/4F2hc) expression in retinal angiogenesis and blood-retina barrier formation.Nature communications · 2024Article
- Transcription factors regulating vasculogenesis and angiogenesis.Developmental dynamics : an official publication of the American Association of Anatomists · 2024Review
- Response of lymphatic endothelial cells to combined spatial and temporal variations in fluid flow.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- MicroRNAs as the critical regulators of Forkhead box protein family during gynecological and breast tumor progression and metastasis.European journal of medical research · 2023Review
- Differential roles of FOXC2 in the trabecular meshwork and Schlemm's canal in glaucomatous pathology.Life science alliance · 2023Article
- Borneol-driven meningeal lymphatic drainage clears amyloid-β peptide to attenuate Alzheimer-like phenotype in mice.Theranostics · 2023Article
- Dysregulated ceramides metabolism by fatty acid 2-hydroxylase exposes a metabolic vulnerability to target cancer metastasis.Signal transduction and targeted therapy · 2022Article
- FOXC2 Promotes Vasculogenic Mimicry in Ovarian Cancer.Cancers · 2022Article
- Low Efficacy of Genetic Tests for the Diagnosis of Primary Lymphedema Prompts Novel Insights into the Underlying Molecular Pathways.International journal of molecular sciences · 2022Article
- CCN2-induced lymphangiogenesis is mediated by the integrin αvβ5-ERK pathway and regulated by DUSP6.Scientific reports · 2022Article
- Mechanical forces in lymphatic vessel development: Focus on transcriptional regulation.Frontiers in physiology · 2022Review
- Fetal nuchal edema and developmental anomalies caused by gene mutations in mice.Frontiers in cell and developmental biology · 2022Review
- The lymphatics in kidney health and disease.Nature reviews. Nephrology · 2021Review
- Molecular Mechanisms of Neuroimmune Crosstalk in the Pathogenesis of Stroke.International journal of molecular sciences · 2021Review
- Article
- A novel SIRT6 activator ameliorates neuroinflammation and ischemic brain injuryActa pharmaceutica Sinica. B · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The lymphatic vasculature is essential for maintaining interstitial fluid homeostasis, and dysfunctional lymphangiogenesis contributes to various pathological processes, including inflammatory disease and tumor metastasis. Mutations in FOXC2 are dominantly associated with late-onset lymphedema; however, the precise role of FOXC2 and a closely related factor, FOXC1, in the lymphatic system remains largely unknown. Here we identified a molecular cascade by which FOXC1 and FOXC2 regulate ERK signaling in lymphatic vessel growth. In mice, lymphatic endothelial cell-specific (LEC-specific) deletion of Foxc1, Foxc2, or both resulted in increased LEC proliferation, enlarged lymphatic vessels, and abnormal lymphatic vessel morphogenesis. Compared with LECs from control animals, LECs from mice lacking both Foxc1 and Foxc2 exhibited aberrant expression of Ras regulators, and embryos with LEC-specific deletion of Foxc1 and Foxc2, alone or in combination, exhibited ERK hyperactivation. Pharmacological ERK inhibition in utero abolished the abnormally enlarged lymphatic vessels in FOXC-deficient embryos. Together, these results identify FOXC1 and FOXC2 as essential regulators of lymphangiogenesis and indicate a new potential mechanistic basis for lymphatic-associated diseases.
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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.