ArticleDevelopment (Cambridge, England)2016
Vegfc acts through ERK to induce sprouting and differentiation of trunk lymphatic progenitors.
Article in Development (Cambridge, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 62 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.
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Who cites it
62 citing papers in PubMed, 102 citations in OpenAlex.
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- Cell death modalities modulate inflammatory and regenerative programs in zebrafish sensory organs.Nature communications · 2026Article
- Single-Cell-Resolution Fate Mapping Reveals Embryonic Venous Origins of Fenestrated Hindbrain Choroid Plexus Vasculature.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Feeder-Free Generation of Lymphatic Endothelial Cells from Human Induced Pluripotent Stem Cells.bioRxiv : the preprint server for biology · 2026Article
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- MultiSite Assembly of Gateway Induced Clones (MAGIC): a flexible cloning toolbox for use in vertebrate model systems.Development (Cambridge, England) · 2025Article
- APOA1 binding protein promotes lymphatic cell fate and lymphangiogenesis by relieving caveolae-mediated inhibition of VEGFR3 signaling.Nature communications · 2025Article
- VEGF signaling promotes blastema growth and proliferation of vascular and non-vascular cells during axolotl limb regeneration.Developmental biology · 2025Article
- Zebrafish Models of Induced Lymphangiogenesis: Current Advancements and Therapeutic Discovery.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Stem and progenitor cell proliferation are independently regulated by cell type-specific cyclinD genes.Nature communications · 2025Article
- Compensatory lymphangiogenesis is required for edema resolution in zebrafish.Scientific reports · 2025Article
- Real-time imaging reveals a role for macrophage protrusive motility in melanoma invasion.The Journal of cell biology · 2025Article
- Endothelial cell transitions in zebrafish vascular development.Development, growth & differentiation · 2024Review
- Multiple cis-regulatory elements control prox1a expression in distinct lymphatic vascular beds.Development (Cambridge, England) · 2024Article
- Central conducting lymphatic anomaly: from bench to bedside.The Journal of clinical investigation · 2024Review
- Lymphatic vessel: origin, heterogeneity, biological functions, and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Generation and application of endogenously floxed alleles for cell-specific knockout in zebrafish.Developmental cell · 2023Article
- Temporospatial inhibition of Erk signaling is required for lymphatic valve formation.Signal transduction and targeted therapy · 2023Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Vascular endothelial growth factor C (Vegfc) activates its receptor, Flt4, to induce lymphatic development. However, the signals that act downstream of Flt4 in this context in vivo remain unclear. To understand Flt4 signaling better, we generated zebrafish bearing a deletion in the Flt4 cytoplasmic domain that eliminates tyrosines Y1226 and 1227. Embryos bearing this deletion failed to initiate sprouting or differentiation of trunk lymphatic vessels and did not form a thoracic duct. Deletion of Y1226/7 prevented ERK phosphorylation in lymphatic progenitors, and ERK inhibition blocked trunk lymphatic sprouting and differentiation. Conversely, endothelial autonomous ERK activation rescued lymphatic sprouting and differentiation in flt4 mutants. Interestingly, embryos bearing the Y1226/7 deletion formed a functional facial lymphatic network enabling them to develop normally to adulthood. By contrast, flt4 null larvae displayed hypoplastic facial lymphatics and severe lymphedema. Thus, facial lymphatic vessels appear to be the first functional lymphatic network in the zebrafish, whereas the thoracic duct is initially dispensable for lymphatic function. Moreover, distinct signaling pathways downstream of Flt4 govern lymphatic morphogenesis and differentiation in different anatomical locations.
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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.