Evidence map›Paper›PMID 25038045›Full record

ArticleDevelopment (Cambridge, England)2014

Hand2 elevates cardiomyocyte production during zebrafish heart development and regeneration.

Yocheved L Schindler, Kristina M Garske, Jinhu Wang, Beth A Firulli, Anthony B Firulli, Kenneth D Poss, Deborah Yelon

Open access · greenAbstract read
In one paragraph

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 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

67 citing papers in PubMed, 131 citations in OpenAlex.

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  17. Myc beyond Cancer: Regulation of Mammalian Tissue Regeneration.Pathophysiology : the official journal of the International Society for Pathophysiology · 2023
    Review
  18. Review
  19. Article
  20. Review

7 more citing papers are in PubMed but not listed here.

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

7 authors at 5 institutions in 1 country.

Yocheved L SchindlerDivision of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA Developmental Genetics Program and Department of Cell Biology, Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.
Kristina M GarskeDivision of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Jinhu WangDepartment of Cell Biology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.
Beth A FirulliRiley Heart Research Center, Herman B. Wells Center for Pediatric Research, Departments of Pediatrics and Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Anthony B FirulliRiley Heart Research Center, Herman B. Wells Center for Pediatric Research, Departments of Pediatrics and Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Kenneth D PossDepartment of Cell Biology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.
Deborah YelonDivision of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA Developmental Genetics Program and Department of Cell Biology, Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA dyelon@ucsd.edu.
Indiana University – Purdue University Indianapolis · USUniversity of California, San Diego · USDuke Medical Center · USHoward Hughes Medical Institute · USNew York University · US

Funding

Regulation of Myocardial Regeneration in ZebrafishR01HL081674 · NHLBI · DUKE UNIVERSITY · PI POSS, KENNETH D · 2005 to 2019
$6.6M
Genetic Regulation of Cardiac Patterning in ZebrafishR01HL069594 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI YELON, DEBORAH · 2002 to 2015
$4.0M
Genetic Regulation of Outflow Tract Formation in ZebrafishR01HL108599 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI YELON, DEBORAH · 2011 to 2019
$3.4M
Endocardial mechanisms of cardiac trabeculation and septationR01HL120920 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI FIRULLI, ANTHONY B. · 2014 to 2017
$1.8M
The role of Twist family bHLH factors in limb morphogenesisR01AR061392 · NIAMS · INDIANA UNIVERSITY INDIANAPOLIS · PI FIRULLI, ANTHONY B. · 2011 to 2015
$1.7M
Cellular and Molecular Mechanisms of Left Ventricular Growth and MorphogenesisR01HL122123 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI FIRULLI, ANTHONY B. · 2014 to 2017
$1.6M
Howard Hughes Medical InstituteNHLBI NIH HHS R01 HL069594NHLBI NIH HHS R01HL069594NHLBI NIH HHS R01 HL081674NHLBI NIH HHS R01HL081674NHLBI NIH HHS R01 HL108599NHLBI NIH HHS R01HL108599NHLBI NIH HHS R01 HL120920NHLBI NIH HHS R01HL120920NHLBI NIH HHS R01 HL122123NHLBI NIH HHS R01HL122123NIAMS NIH HHS R01 AR061392NIAMS NIH HHS R01AR061392
6 · The paper itself

Abstract

Embryonic heart formation requires the production of an appropriate number of cardiomyocytes; likewise, cardiac regeneration following injury relies upon the recovery of lost cardiomyocytes. The basic helix-loop-helix (bHLH) transcription factor Hand2 has been implicated in promoting cardiomyocyte formation. It is unclear, however, whether Hand2 plays an instructive or permissive role during this process. Here, we find that overexpression of hand2 in the early zebrafish embryo is able to enhance cardiomyocyte production, resulting in an enlarged heart with a striking increase in the size of the outflow tract. Our evidence indicates that these increases are dependent on the interactions of Hand2 in multimeric complexes and are independent of direct DNA binding by Hand2. Proliferation assays reveal that hand2 can impact cardiomyocyte production by promoting division of late-differentiating cardiac progenitors within the second heart field. Additionally, our data suggest that hand2 can influence cardiomyocyte production by altering the patterning of the anterior lateral plate mesoderm, potentially favoring formation of the first heart field at the expense of hematopoietic and vascular lineages. The potency of hand2 during embryonic cardiogenesis suggested that hand2 could also impact cardiac regeneration in adult zebrafish; indeed, we find that overexpression of hand2 can augment the regenerative proliferation of cardiomyocytes in response to injury. Together, our studies demonstrate that hand2 can drive cardiomyocyte production in multiple contexts and through multiple mechanisms. These results contribute to our understanding of the potential origins of congenital heart disease and inform future strategies in regenerative medicine.

Indexed as

Gene Expression Regulation, DevelopmentalAmino Acid SequenceAnimalsBasic Helix-Loop-Helix ProteinsCell ProliferationDNAGene Expression ProfilingGenotypeHeartIn Situ HybridizationIn Situ Hybridization, FluorescenceMiceMolecular Sequence DataMyocytes, CardiacRegenerationSequence Homology, Amino AcidBasic Helix-Loop-Helix ProteinsDNAhand2 protein, zebrafishZebrafish ProteinsCardiac regenerationFirst heart fieldHand2Second heart fieldZebrafish

Identifiers

PMID25038045
PMCPMC4197543
OpenAlexW2026636180

What OpenQuestion holds

Textmetadata
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.