ArticleThe Journal of clinical investigation2013
Endothelial ERK signaling controls lymphatic fate specification.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.
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.
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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
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 137 citations in OpenAlex.
- Trametinib as a targeted treatment in cardiac and lymphatic presentations of Noonan syndrome.Frontiers in pediatrics · 2025Pooled it
- Signaling scaffold Shoc2 regulates lymphangiogenesis by suppressing mTORC1-mediated IFN responses.Cell death and differentiation · 2026Article
- Ultrasmall inorganic nanoparticles repair damaged meningeal lymphatic vessels to boost Parkinson's disease therapy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Zebrafish Models of Induced Lymphangiogenesis: Current Advancements and Therapeutic Discovery.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Targeted Therapy for Complex Lymphatic Anomalies in Patients with Noonan Syndrome and Related Disorders.International journal of molecular sciences · 2025Article
- Meningeal lymphatic drainage: novel insights into central nervous system disease.Signal transduction and targeted therapy · 2025Review
- Intratumoral Collagen Deposition Supports Angiogenesis Suggesting Anti-angiogenic Therapy in Armored and Cold Tumors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- From bench to bedside: murine models of inherited and sporadic brain arteriovenous malformations.Angiogenesis · 2025Review
- Regulation of VEGFR3 signaling in lymphatic endothelial cells.Frontiers in cell and developmental biology · 2025Review
- Bridging the Gap: Endothelial Dysfunction and the Role of iPSC-Derived Endothelial Cells in Disease Modeling.International journal of molecular sciences · 2024Review
- EPHB4-RASA1 Inhibition of PIEZO1 Ras Activation Drives Lymphatic Valvulogenesis.Circulation research · 2024Article
- Inactivation of ERK1/2 signaling mediates dysfunction of basal meningeal lymphatic vessels in experimental subdural hematoma.Theranostics · 2024Article
- Review
- An EPHB4-RASA1 signaling complex inhibits shear stress-induced Ras-MAPK activation in lymphatic endothelial cells to promote the development of lymphatic vessel valves.bioRxiv : the preprint server for biology · 2023Article
- Temporospatial inhibition of Erk signaling is required for lymphatic valve formation.Signal transduction and targeted therapy · 2023Article
- Single-cell analysis of lymphatic endothelial cell fate specification and differentiation during zebrafish development.The EMBO journal · 2023Article
- Review
- Lymphatic anomalies during lifetime in patients with Noonan syndrome: Retrospective cohort study.American journal of medical genetics. Part A · 2022Article
- Molecular Mechanisms Driving Lymphedema and Other Lymphatic Anomalies.Cold Spring Harbor perspectives in medicine · 2022Article
- Expression Profile of CD157 Reveals Functional Heterogeneity of Capillaries in Human Dermal Skin.Biomedicines · 2022Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Lymphatic vessels are thought to arise from PROX1-positive endothelial cells (ECs) in the cardinal vein in response to induction of SOX18 expression; however, the molecular event responsible for increased SOX18 expression has not been established. We generated mice with endothelial-specific, inducible expression of an RAF1 gene with a gain-of-function mutation (RAF1(S259A)) that is associated with Noonan syndrome. Expression of mutant RAF1(S259A) in ECs activated ERK and induced SOX18 and PROX1 expression, leading to increased commitment of venous ECs to the lymphatic fate. Excessive production of lymphatic ECs resulted in lymphangiectasia that was highly reminiscent of abnormal lymphatics seen in Noonan syndrome and similar "RASopathies." Inhibition of ERK signaling during development abrogated the lymphatic differentiation program and rescued the lymphatic phenotypes induced by expression of RAF1(S259A). These data suggest that ERK activation plays a key role in lymphatic EC fate specification and that excessive ERK activation is the basis of lymphatic abnormalities seen in Noonan syndrome and related 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.