ArticleNature communications2015
Alk1 and Alk5 inhibition by Nrp1 controls vascular sprouting downstream of Notch.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.
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Who cites it
108 citing papers in PubMed, 168 citations in OpenAlex.
- Cell-to-Cell Signaling Networks at the Blood-Brain Barrier in Health and Disease.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
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- Blood and lymphatic vascular network in bone injury repair: from molecular mechanisms to therapeutic strategies.Science China. Life sciences · 2026Review
- CreER activation transiently disrupts angiogenesis by reducing proliferation and promoting apoptosis in vascular endothelial cells.Angiogenesis · 2026Article
- Neuropilin 1 (NRP1) conveys SEMA3A signals to restrict physiological angiogenesis.Angiogenesis · 2026Article
- Development of the blood-brain barrier.Development (Cambridge, England) · 2026Review
- PIEZO1 Overexpression in Hereditary Hemorrhagic Telangiectasia Arteriovenous Malformations.Circulation · 2025Article
- Dissecting endothelial cell heterogeneity with new tools.Cell regeneration (London, England) · 2025Review
- Article
- A non-genetic model of vascular shunts informs on the cellular mechanisms of formation and resolution of arteriovenous malformations.Cardiovascular research · 2024Article
- ACVR1/ALK2-p21 signaling axis modulates proliferation of the venous endothelium in the retinal vasculature.Angiogenesis · 2024Article
- Methylome analysis of endothelial cells suggests new insights on sporadic brain arteriovenous malformation.Heliyon · 2024Article
- SLC44A2 regulates vascular smooth muscle cell phenotypic switching and aortic aneurysm.The Journal of clinical investigation · 2024Article
- Endothelial Neuropilin-1: a multifaced signal transducer with an emerging role in inflammation and atherosclerosis beyond angiogenesis.Biochemical Society transactions · 2024Review
- SUMOylation Fine-Tunes Endothelial HEY1 in the Regulation of Angiogenesis.Circulation research · 2024Article
- A secreted proteomic footprint for stem cell pluripotency.PloS one · 2024Article
- Biology of vascular mural cells.Development (Cambridge, England) · 2023Review
- Regulation of Notch1 Signalling by Long Non-Coding RNAs in Cancers and Other Health Disorders.International journal of molecular sciences · 2023Review
- Fibrillin-1 regulates endothelial sprouting during angiogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Endothelial tip/stalk cell selection requires BMP9-induced βMolecular biology of the cell · 2023Article
48 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
15 authors at 8 institutions in 6 countries.
Funding
Abstract
Sprouting angiogenesis drives blood vessel growth in healthy and diseased tissues. Vegf and Dll4/Notch signalling cooperate in a negative feedback loop that specifies endothelial tip and stalk cells to ensure adequate vessel branching and function. Current concepts posit that endothelial cells default to the tip-cell phenotype when Notch is inactive. Here we identify instead that the stalk-cell phenotype needs to be actively repressed to allow tip-cell formation. We show this is a key endothelial function of neuropilin-1 (Nrp1), which suppresses the stalk-cell phenotype by limiting Smad2/3 activation through Alk1 and Alk5. Notch downregulates Nrp1, thus relieving the inhibition of Alk1 and Alk5, thereby driving stalk-cell behaviour. Conceptually, our work shows that the heterogeneity between neighbouring endothelial cells established by the lateral feedback loop of Dll4/Notch utilizes Nrp1 levels as the pivot, which in turn establishes differential responsiveness to TGF-β/BMP signalling.
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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.