ArticleDevelopment (Cambridge, England)2024
Multiple cis-regulatory elements control prox1a expression in distinct lymphatic vascular beds.
Article in Development (Cambridge, England), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 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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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
6 citing papers in PubMed.
- 3D chromatin organisation contributes to the regulatory logic in differentiating lymphatic endothelium.EMBO reports · 2026Article
- Lymphatic Endothelial Cells in Health and Disease.MedComm · 2026Review
- TGFβ signaling promotes cell cycle progression and resistance to the CDK4/6 inhibitor palbociclib through SOX4 transcriptional modulation in breast cancer cells.Cell death & disease · 2026Article
- Zebrafish Models of Induced Lymphangiogenesis: Current Advancements and Therapeutic Discovery.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Direct specification of lymphatic endothelium from mesenchymal progenitors.Nature cardiovascular research · 2025Article
- Mechanisms of Cancer Cell Lymphatic Endothelialization in Tumor Lymphangiogenesis and Metastasis: A Comprehensive Review.Journal of inflammation research · 2025Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
During embryonic development, lymphatic endothelial cell (LEC) precursors are distinguished from blood endothelial cells by the expression of Prospero-related homeobox 1 (Prox1), which is essential for lymphatic vasculature formation in mouse and zebrafish. Prox1 expression initiation precedes LEC sprouting and migration, serving as the marker of specified LECs. Despite its crucial role in lymphatic development, Prox1 upstream regulation in LECs remains to be uncovered. SOX18 and COUP-TFII are thought to regulate Prox1 in mice by binding its promoter region. However, the specific regulation of Prox1 expression in LECs remains to be studied in detail. Here, we used evolutionary conservation and chromatin accessibility to identify enhancers located in the proximity of zebrafish prox1a active in developing LECs. We confirmed the functional role of the identified sequences through CRISPR/Cas9 mutagenesis of a lymphatic valve enhancer. The deletion of this region results in impaired valve morphology and function. Overall, our results reveal an intricate control of prox1a expression through a collection of enhancers. Ray-finned fish-specific distal enhancers drive pan-lymphatic expression, whereas vertebrate-conserved proximal enhancers refine expression in functionally distinct subsets of lymphatic endothelium.
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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 Socratic graph.