ArticleBlood2010
RapGEF2 is essential for embryonic hematopoiesis but dispensable for adult hematopoiesis.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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
24 citing papers in PubMed, 44 citations in OpenAlex.
- Susceptibility to Childhood Pneumonia: A Genome-Wide Analysis.American journal of respiratory cell and molecular biology · 2017Trial
- Replication and hematological characterization of human platelet reactivity genetic associations in men from the Caerphilly Prospective Study (CaPS).Journal of thrombosis and thrombolysis · 2016Trial
- A novel G13-RAPGEF2-RAP1 signaling pathway critical for platelet adhesion and aggregation.Blood · 2026Article
- Article
- Nucleated red blood cells explain most of the association between DNA methylation and gestational age.Communications biology · 2023Article
- Host T Cell Dedifferentiation Effects Drive HIV-1 Latency Stability.Journal of virology · 2022Article
- The functional genetic architecture of egg-laying and live-bearing reproduction in common lizards.Nature ecology & evolution · 2021Article
- Transcriptional and epigenetic landscape of CaJournal of cell communication and signaling · 2021Article
- ARHGEF12 regulates erythropoiesis and is involved in erythroid regeneration after chemotherapy in acute lymphoblastic leukemia patients.Haematologica · 2020Article
- Location, Location, Location: How Vascular Specialization Influences Hematopoietic Fates During Development.Frontiers in cell and developmental biology · 2020Review
- Transforming Endothelium with Platelet-Rich Plasma in Engineered Microvessels.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2019Article
- Endothelial PKA activity regulates angiogenesis by limiting autophagy through phosphorylation of ATG16L1.eLife · 2019Article
- Disruption of MAGI2-RapGEF2-Rap1 signaling contributes to podocyte dysfunction in congenital nephrotic syndrome caused by mutations in MAGI2.Kidney international · 2019Article
- Rap1 signal modulators control the maintenance of hematopoietic progenitors in bone marrow and adult long-term hematopoiesis.Cancer science · 2019Article
- Small GTPase Rap1A/B Is Required for Lymphatic Development and Adrenomedullin-Induced Stabilization of Lymphatic Endothelial Junctions.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- Dpp dependent Hematopoietic stem cells give rise to Hh dependent blood progenitors in larval lymph gland ofeLife · 2016Article
- Developmental checkpoints guarded by regulated necrosis.Cellular and molecular life sciences : CMLS · 2016Review
- Dynamic Gene Regulatory Networks Drive Hematopoietic Specification and Differentiation.Developmental cell · 2016Article
- Substrate trapping proteomics reveals targets of the βTrCP2/FBXW11 ubiquitin ligase.Molecular and cellular biology · 2015Article
- Rap1 signaling in endothelial barrier control.Cell adhesion & migration · 2014Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
RapGEF2 is one of many guanine nucleotide exchange factors (GEFs) that specifically activate Rap1. Here, we generated RapGEF2 conditional knockout mice and studied its role in embryogenesis and fetal as well as adult hematopoietic stem cell (HSC) regulation. RapGEF2 deficiency led to embryonic lethality at ~ E11.5 due to severe yolk sac vascular defects. However, a similar number of Flk1(+) cells were present in RapGEF2(+/+) and RapGEF2(-/-) yolk sacs indicating that the bipotential early progenitors were in fact generated in the absence of RapGEF2. Further analysis of yolk sacs and embryos revealed a significant reduction of CD41 expressing cells in RapGEF2(-/-) genotype, suggesting a defect in the maintenance of definitive hematopoiesis. RapGEF2(-/-) cells displayed defects in proliferation and migration, and the in vitro colony formation ability of hematopoietic progenitors was also impaired. At the molecular level, Rap1 activation was impaired in RapGEF2(-/-) cells that in turn lead to defective B-raf/ERK signaling. Scl/Gata transcription factor expression was significantly reduced, indicating that the defects observed in RapGEF2(-/-) cells could be mediated through Scl/Gata deregulation. Inducible deletion of RapGEF2 during late embryogenesis in RapGEF2(cko/cko)ER(cre) mice leads to defective fetal liver erythropoiesis. Conversely, inducible deletion in the adult bone marrow, or specific deletion in B cells, T cells, HSCs, and endothelial cells has no impact on hematopoiesis.
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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.