ArticleDevelopment (Cambridge, England)2014
Deletion of Rbpj from postnatal endothelium leads to abnormal arteriovenous shunting in mice.
Article in Development (Cambridge, England), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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.
The trial behind it
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
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Translational relevance of animal models available on brain arteriovenous malformations, a systematic review.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Pooled it
- Towards precision medicine for brain arteriovenous malformations.The Journal of clinical investigation · 2026Review
- Decoding brain arteriovenous malformations: from genetic insights to modeling the vascular maze.Acta neuropathologica communications · 2026Review
- Advances in the Genetics and Molecular Biology of Brain Arteriovenous Malformations.Translational stroke research · 2026Review
- Bmp9 regulates Notch signaling and the temporal dynamics of angiogenesis via Lunatic Fringe.Developmental cell · 2026Article
- Diverse roles of connexins in the neuro-vasculature in homeostasis and disease.Translational neuroscience · 2026Review
- Characterizing the Microenvironment of Cerebral Arteriovenous Malformations to Test Novel Treatment Modalities.Brain sciences · 2025Review
- Notch4 is essential for the maintenance of vascular homeostasis in the young adult pituitary posterior lobes.Scientific reports · 2025Article
- From bench to bedside: murine models of inherited and sporadic brain arteriovenous malformations.Angiogenesis · 2025Review
- CNS resident macrophages exhibit region-specific states and immunogenic responses during Rbpj-deficient brain arteriovenous malformation.Scientific reports · 2025Article
- Methylome analysis of endothelial cells suggests new insights on sporadic brain arteriovenous malformation.Heliyon · 2024Article
- Transcription factors regulating vasculogenesis and angiogenesis.Developmental dynamics : an official publication of the American Association of Anatomists · 2024Review
- A new fasciocutaneous flap model identifies a critical role for endothelial Notch signaling in wound healing and flap survival.Scientific reports · 2023Article
- Endothelial Rbpj Is Required for Cerebellar Morphogenesis and Motor Control in the Early Postnatal Mouse Brain.Cerebellum (London, England) · 2023Article
- miR-342-5p downstream to Notch enhances arterialization of endothelial cells in response to shear stress by repressing MYC.Molecular therapy. Nucleic acids · 2023Article
- Article
- Nitric oxide synthase and reduced arterial tone contribute to arteriovenous malformation.Science advances · 2023Article
- Notch Signaling in Acute Inflammation and Sepsis.International journal of molecular sciences · 2023Review
- Endothelial Rbpj deletion normalizes Notch4-induced brain arteriovenous malformation in mice.The Journal of experimental medicine · 2023Article
- Pericytes and vascular smooth muscle cells in central nervous system arteriovenous malformations.Frontiers in physiology · 2023Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Arteriovenous malformations (AVMs) are tortuous vessels characterized by arteriovenous (AV) shunts, which displace capillaries and shunt blood directly from artery to vein. Notch signaling regulates embryonic AV specification by promoting arterial, as opposed to venous, endothelial cell (EC) fate. To understand the essential role of endothelial Notch signaling in postnatal AV organization, we used inducible Cre-loxP recombination to delete Rbpj, a mediator of canonical Notch signaling, from postnatal ECs in mice. Deletion of endothelial Rbpj from birth resulted in features of AVMs by P14, including abnormal AV shunting and tortuous vessels in the brain, intestine and heart. We further analyzed brain AVMs, as they pose particular health risks. Consistent with AVM pathology, we found cerebral hemorrhage, hypoxia and necrosis, and neurological deficits. AV shunts originated from capillaries (and possibly venules), with the earliest detectable morphological abnormalities in AV connections by P8. Prior to AV shunt formation, alterations in EC gene expression were detected, including decreased Efnb2 and increased Pai1, which encodes a downstream effector of TGFβ signaling. After AV shunts had formed, whole-mount immunostaining showed decreased Efnb2 and increased Ephb4 expression within AV shunts, suggesting that ECs were reprogrammed from arterial to venous identity. Deletion of Rbpj from adult ECs led to tortuosities in gastrointestinal, uterine and skin vascular beds, but had mild effects in the brain. Our results demonstrate a temporal requirement for Rbpj in postnatal ECs to maintain proper artery, capillary and vein organization and to prevent abnormal AV shunting and AVM pathogenesis.
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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.