Evidence map›Paper›PMID 25722433›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2015

Etv2 and fli1b function together as key regulators of vasculogenesis and angiogenesis.

Michael P Craig, Viktorija Grajevskaja, Hsin-Kai Liao, Jorune Balciuniene, Stephen C Ekker, Joo-Seop Park, Jeffrey J Essner, Darius Balciunas, Saulius Sumanas

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
4.5field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

44 citing papers in PubMed, 63 citations in OpenAlex.

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  7. Embryology of the Vascular System: Implications for Variants.Seminars in interventional radiology · 2025
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  10. Zebrafish: a convenient tool for myelopoiesis research.Cell regeneration (London, England) · 2023
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  11. Learning from Zebrafish Hematopoiesis.Advances in experimental medicine and biology · 2023
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  14. Blastocyst complementation and interspecies chimeras in gene edited pigs.Frontiers in cell and developmental biology · 2022
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  15. Review
  16. Article
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  19. Zebrafish etv2 knock-in line labels vascular endothelial and blood progenitor cells.Developmental dynamics : an official publication of the American Association of Anatomists · 2020
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Michael P CraigFrom the Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, OH (M.P.C.); Division of Developmental Biology (M.P.C., J.-S.P.), Department of Pediatrics (S.S.), Department of Pediatric Urology (J.-S.P.), Cincinnati Children's Hospital Medical Center, OH; Department of Biology, Temple University, Philadelphia, PA (V.G., J.B., D.B.); Department of Genetics, Development and Cell Biology, Iowa State University, Ames (H.-K.L., J.J.E.); Department of Zoology, Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania (V.G.); and Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN (S.C.E.).
Viktorija GrajevskajaFrom the Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, OH (M.P.C.); Division of Developmental Biology (M.P.C., J.-S.P.), Department of Pediatrics (S.S.), Department of Pediatric Urology (J.-S.P.), Cincinnati Children's Hospital Medical Center, OH; Department of Biology, Temple University, Philadelphia, PA (V.G., J.B., D.B.); Department of Genetics, Development and Cell Biology, Iowa State University, Ames (H.-K.L., J.J.E.); Department of Zoology, Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania (V.G.); and Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN (S.C.E.).
Hsin-Kai LiaoFrom the Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, OH (M.P.C.); Division of Developmental Biology (M.P.C., J.-S.P.), Department of Pediatrics (S.S.), Department of Pediatric Urology (J.-S.P.), Cincinnati Children's Hospital Medical Center, OH; Department of Biology, Temple University, Philadelphia, PA (V.G., J.B., D.B.); Department of Genetics, Development and Cell Biology, Iowa State University, Ames (H.-K.L., J.J.E.); Department of Zoology, Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania (V.G.); and Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN (S.C.E.).
Jorune BalciunieneFrom the Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, OH (M.P.C.); Division of Developmental Biology (M.P.C., J.-S.P.), Department of Pediatrics (S.S.), Department of Pediatric Urology (J.-S.P.), Cincinnati Children's Hospital Medical Center, OH; Department of Biology, Temple University, Philadelphia, PA (V.G., J.B., D.B.); Department of Genetics, Development and Cell Biology, Iowa State University, Ames (H.-K.L., J.J.E.); Department of Zoology, Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania (V.G.); and Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN (S.C.E.).
Stephen C EkkerFrom the Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, OH (M.P.C.); Division of Developmental Biology (M.P.C., J.-S.P.), Department of Pediatrics (S.S.), Department of Pediatric Urology (J.-S.P.), Cincinnati Children's Hospital Medical Center, OH; Department of Biology, Temple University, Philadelphia, PA (V.G., J.B., D.B.); Department of Genetics, Development and Cell Biology, Iowa State University, Ames (H.-K.L., J.J.E.); Department of Zoology, Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania (V.G.); and Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN (S.C.E.).
Joo-Seop ParkFrom the Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, OH (M.P.C.); Division of Developmental Biology (M.P.C., J.-S.P.), Department of Pediatrics (S.S.), Department of Pediatric Urology (J.-S.P.), Cincinnati Children's Hospital Medical Center, OH; Department of Biology, Temple University, Philadelphia, PA (V.G., J.B., D.B.); Department of Genetics, Development and Cell Biology, Iowa State University, Ames (H.-K.L., J.J.E.); Department of Zoology, Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania (V.G.); and Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN (S.C.E.).
Jeffrey J EssnerFrom the Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, OH (M.P.C.); Division of Developmental Biology (M.P.C., J.-S.P.), Department of Pediatrics (S.S.), Department of Pediatric Urology (J.-S.P.), Cincinnati Children's Hospital Medical Center, OH; Department of Biology, Temple University, Philadelphia, PA (V.G., J.B., D.B.); Department of Genetics, Development and Cell Biology, Iowa State University, Ames (H.-K.L., J.J.E.); Department of Zoology, Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania (V.G.); and Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN (S.C.E.).
Darius BalciunasFrom the Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, OH (M.P.C.); Division of Developmental Biology (M.P.C., J.-S.P.), Department of Pediatrics (S.S.), Department of Pediatric Urology (J.-S.P.), Cincinnati Children's Hospital Medical Center, OH; Department of Biology, Temple University, Philadelphia, PA (V.G., J.B., D.B.); Department of Genetics, Development and Cell Biology, Iowa State University, Ames (H.-K.L., J.J.E.); Department of Zoology, Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania (V.G.); and Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN (S.C.E.).
Saulius SumanasFrom the Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, OH (M.P.C.); Division of Developmental Biology (M.P.C., J.-S.P.), Department of Pediatrics (S.S.), Department of Pediatric Urology (J.-S.P.), Cincinnati Children's Hospital Medical Center, OH; Department of Biology, Temple University, Philadelphia, PA (V.G., J.B., D.B.); Department of Genetics, Development and Cell Biology, Iowa State University, Ames (H.-K.L., J.J.E.); Department of Zoology, Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania (V.G.); and Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN (S.C.E.). Saulius.Sumanas@cchmc.org.
University of Cincinnati Medical Center · USVilnius University · LTIowa State University · US

Funding

Systematic Vertebrate Functional GenomicsR01GM063904 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI EKKER, STEPHEN CARL · 2001 to 2025
$10.7M
Pulmonary Development and Disease Pathogenesis Training ProgramT32HL007752 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI Francis Xavier McCormack, Anne-Karina Theresia Perl · 1994 to 2026
$6.3M
Intron-based Mutagenic Transposons for ZebrafishR01DA014546 · NIDA · UNIVERSITY OF MINNESOTA TWIN CITIES · PI EKKER, STEPHEN CARL · 2001 to 2011
$3.5M
Molecular Mechanisms of Arterial-Venous Differentiation in ZebrafishR01HL107369 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI SUMANAS, SAULIUS · 2011 to 2015
$1.9M
Cell Fate Regulation of Nephron ProgenitorsR01DK100315 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI PARK, JOO-SEOP · 2014 to 2018
$1.7M
Transposon-based Platform for Insertional Mutagenesis and Genome EngineeringR01HD061749 · NICHD · TEMPLE UNIV OF THE COMMONWEALTH · PI BALCIUNAS, DARIUS · 2010 to 2014
$1.5M
In vitro and in vivo Signaling Mechanisms during Endothelial Tube FormationR01GM088424 · NIGMS · IOWA STATE UNIVERSITY · PI ESSNER, JEFFREY J · 2011 to 2015
$1.3M
Systematic Vertebrate Functional GenomicsR56GM063904 · NIGMS · MAYO CLINIC ROCHESTER · PI EKKER, STEPHEN CARL · 2009 to 2010
$611k
NHLBI NIH HHS 5T32HL007752-18NHLBI NIH HHS HL107369NHLBI NIH HHS R01 HL107369NHLBI NIH HHS T32 HL007752NICHD NIH HHS R01 HD061749NIDA NIH HHS DA14546NIDA NIH HHS R01 DA014546NIDDK NIH HHS DK100325NIDDK NIH HHS R01 DK100315NIGMS NIH HHS GM63904NIGMS NIH HHS R01 GM063904NIGMS NIH HHS R01 GM088424NIGMS NIH HHS R56 GM063904
6 · The paper itself

Abstract

objectiveThe E26 transformation-specific domain transcription factor Etv2/Etsrp/ER71 is a master regulator of vascular endothelial differentiation during vasculogenesis, although its later role in sprouting angiogenesis remains unknown. Here, we investigated in the zebrafish model a role for Etv2 and related E26 transformation-specific factors, Fli1a and Fli1b in developmental angiogenesis. APPROACH AND

resultsZebrafish fli1a and fli1b mutants were obtained using transposon-mediated gene trap approach. Individual fli1a and fli1b homozygous mutant embryos display normal vascular patterning, yet the angiogenic recovery observed in older etv2 mutant embryos does not occur in embryos lacking both etv2 and fli1b. Etv2 and fli1b double-deficient embryos fail to form any angiogenic sprouts and show greatly increased apoptosis throughout the axial vasculature. In contrast, fli1a mutation did not affect the recovery of etv2 mutant phenotype. Overexpression analyses indicate that both etv2 and fli1b, but not fli1a, induce the expression of multiple vascular markers and of each other. Temporal inhibition of Etv2 function using photoactivatable morpholinos indicates that the function of Etv2 and Fli1b during angiogenesis is independent from the early requirement of Etv2 during vasculogenesis. RNA-Seq analysis and chromatin immunoprecipitation suggest that Etv2 and Fli1b share the same transcriptional targets and bind to the same E26 transformation-specific sites.

conclusionsOur data argue that there are 2 phases of early vascular development with distinct requirements of E26 transformation-specific transcription factors. Etv2 alone is required for early vasculogenesis, whereas Etv2 and Fli1b function redundantly during late vasculogenesis and early embryonic angiogenesis.

Indexed as

Neovascularization, PhysiologicAngiogenic ProteinsAnimalsAnimals, Genetically ModifiedApoptosisBinding SitesEmbryo, NonmammalianEndothelial CellsGene Expression Regulation, DevelopmentalGenotypeMorpholinosMutationPhenotypePromoter Regions, GeneticProto-Oncogene Protein c-fli-1Signal TransductionAngiogenic ProteinsEtv2 protein, zebrafishFli1b protein, zebrafishMorpholinosProto-Oncogene Protein c-fli-1Transcription FactorsZebrafish ProteinsangiogenesisETS transcription factorvasculogenesiszebrafish

Identifiers

PMID25722433
PMCPMC4427907
OpenAlexW2157437573

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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.