Evidence map›Paper›PMID 25536398›Full record

ArticleDevelopmental biology2015

An early requirement for nkx2.5 ensures the first and second heart field ventricular identity and cardiac function into adulthood.

Vanessa George, Sophie Colombo, Kimara L Targoff

Open access · greenAbstract read
In one paragraph

Article in Developmental biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 9% 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

46 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.

  1. Pooled it
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  17. Mutational Assessment inInternational journal of environmental research and public health · 2022
    Article
  18. Article
  19. Modeling Human Cardiac Arrhythmias: Insights from Zebrafish.Journal of cardiovascular development and disease · 2022
    Review
  20. AnFrontiers in cardiovascular medicine · 2022
    Article
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

3 authors at 1 institution in 1 country.

Vanessa GeorgeDivision of Pediatric Cardiology, Department of Pediatrics, College of Physicians & Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032 USA.
Sophie ColomboDivision of Pediatric Cardiology, Department of Pediatrics, College of Physicians & Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032 USA.
Kimara L TargoffDivision of Pediatric Cardiology, Department of Pediatrics, College of Physicians & Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032 USA. Electronic address: kl284@columbia.edu.
Columbia University · US

Funding

CHILD HEALTH RESEARCH CENTER CAREER DEVELOPMENT AWARDK12HD043389 · NICHD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI DRISCOLL, JOHN M · 2003 to 2007
$2.2M
Regulation of cardiac morphogenesis by Nkx genes in the zebrafish embryoK08HL088002 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI TARGOFF, KIMARA L · 2007 to 2010
$517k
NHLBI NIH HHS K08 HL088002NICHD NIH HHS K12 HD043389NICHD NIH HHS K12HD043389
6 · The paper itself

Abstract

Temporally controlled mechanisms that define the unique features of ventricular and atrial cardiomyocyte identities are essential for the construction of a coordinated, morphologically intact heart. We have previously demonstrated an important role for nkx genes in maintaining ventricular identity, however, the specific timing of nkx2.5 function in distinct cardiomyocyte populations has yet to be elucidated. Here, we show that heat-shock induction of a novel transgenic line, Tg(hsp70l:nkx2.5-EGFP), during the initial stages of cardiomyocyte differentiation leads to rescue of chamber shape and identity in nkx2.5(-/-) embryos as chambers emerge. Intriguingly, our findings link an early role of this essential cardiac transcription factor with a later function. Moreover, these data reveal that nkx2.5 is also required in the second heart field as the heart tube forms, reflecting the temporal delay in differentiation of this population. Thus, our results support a model in which nkx genes induce downstream targets that are necessary to maintain chamber-specific identity in both early- and late-differentiating cardiomyocytes at discrete stages in cardiac morphogenesis. Furthermore, we show that overexpression of nkx2.5 during the first and second heart field development not only rescues the mutant phenotype, but also is sufficient for proper function of the adult heart. Taken together, these results shed new light on the stage-dependent mechanisms that sculpt chamber-specific cardiomyocytes and, therefore, have the potential to improve in vitro generation of ventricular cells to treat myocardial infarction and congenital heart disease.

Indexed as

AnimalsBlotting, WesternCell CountCell DifferentiationDNA PrimersGene Expression Regulation, DevelopmentalGene Knockout TechniquesGenotypeGreen Fluorescent ProteinsHeart VentriclesHomeobox Protein Nkx-2.5Image Processing, Computer-AssistedIn Situ HybridizationMicroscopy, FluorescenceMorphogenesisMyocytes, CardiacDNA Primersenhanced green fluorescent proteinGreen Fluorescent ProteinsHomeobox Protein Nkx-2.5Nkx2.5 protein, zebrafishTranscription FactorsZebrafish ProteinsAtriumChamber identitynkx2.5nkx2.7VentricleZebrafish

Identifiers

PMID25536398
PMCPMC4361364
OpenAlexW2054862213

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.