ArticleDevelopmental biology2016
Segregated Foxc2, NFATc1 and Connexin expression at normal developing venous valves, and Connexin-specific differences in the valve phenotypes of Cx37, Cx43, and Cx47 knockout mice.
Article in Developmental biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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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.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- The role of the cardiac lymphatic system in heart failure "reverse remodeling": from developmental signals to druggable targets.Frontiers in immunology · 2026Review
- Venous Tone is a Critical Determinant of Venous Valve Closure in the Mouse.Function (Oxford, England) · 2025Article
- Hierarchical Requirement for Endothelial Cell Connexins Cx37, Cx47, Cx43, and Cx45 in Lymphatic Valve Function.Function (Oxford, England) · 2025Article
- Molecular dynamics simulation of GJC2 mutants reveal pathogenic mechanisms of PMLD1 and SPG44.The Journal of general physiology · 2025Article
- Clinical Relevance of Animal Models of Lymphatic Dysfunction and Lymphedema.Microcirculation (New York, N.Y. : 1994) · 2025Review
- IL6/adiponectin/HMGB1 feedback loop mediates adipocyte and macrophage crosstalk and M2 polarization after myocardial infarction.Frontiers in immunology · 2024Article
- 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
- Connexin and Pannexin Large-Pore Channels in Microcirculation and Neurovascular Coupling Function.International journal of molecular sciences · 2022Review
- Connexin Expression Is Altered in Liver Development ofInternational journal of molecular sciences · 2021Article
- Mutations in EPHB4 cause human venous valve aplasia.JCI insight · 2021Article
- Biochemical and mechanical signals in the lymphatic vasculature.Cellular and molecular life sciences : CMLS · 2021Review
- The BMP Pathway in Blood Vessel and Lymphatic Vessel Biology.International journal of molecular sciences · 2021Review
- Lymphatic Connexins and Pannexins in Health and Disease.International journal of molecular sciences · 2021Review
- Abnormal lymphatic phenotype in a CRISPR mouse model of the human lymphedema-causing Connexin47 R260C point mutation.Lymphology · 2021Article
- YAP and TAZ maintain PROX1 expression in the developing lymphatic and lymphovenous valves in response to VEGF-C signaling.Development (Cambridge, England) · 2020Article
- RASA1-driven cellular export of collagen IV is required for the development of lymphovenous and venous valves in mice.Development (Cambridge, England) · 2020Article
- Lymphatic Endothelial Cell Junctions: Molecular Regulation in Physiology and Diseases.Frontiers in physiology · 2020Review
- Endothelial Cell Development and Its Application to Regenerative Medicine.Circulation research · 2019Review
- Adrenomedullin Induces Cardiac Lymphangiogenesis After Myocardial Infarction and Regulates Cardiac Edema Via Connexin 43.Circulation research · 2019Article
- Endothelial connexins in vascular function.Vascular biology (Bristol, England) · 2019Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Venous valves (VVs) are critical for unidirectional blood flow from superficial and deep veins towards the heart. Congenital valve aplasia or agenesis may, in some cases, be a direct cause of vascular disease, motivating an understanding of the molecular mechanisms underlying the development and maintenance of VVs. Three gap junction proteins (Connexins), Cx37, Cx43, and Cx47, are specifically expressed at VVs in a highly polarized fashion. VVs are absent from adult mice lacking Cx37; however it is not known if Cx37 is required for the initial formation of valves. In addition, the requirement of Cx43 and Cx47 for VV development has not been studied. Here, we provide a detailed description of Cx37, Cx43, and Cx47 expression during mouse vein development and show by gene knockout that each Cx is necessary for normal valve development. The valve phenotypes in the knockout lines exhibit Cx-specific differences, however, including whether peripheral or central VVs are affected by gene inactivation. In addition, we show that a Cx47 null mutation impairs peripheral VV development but does not affect lymphatic valve formation, a finding of significance for understanding how some CX47 mutations cause inherited lymphedema in humans. Finally, we demonstrate a striking segregation of Foxc2 and NFATc1 transcription factor expression between the downstream and upstream faces, respectively, of developing VV leaflets and show that this segregation is closely associated with the highly polarized expression of Cx37, Cx43, and Cx47. The partition of Foxc2 and NFATc1 expression at VV leaflets makes it unlikely that these factors directly cooperate during the leaflet elongation stage of VV development.
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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.