PUBLICATION

Hand2 elevates cardiomyocyte production during zebrafish heart development and regeneration

Authors
Schindler, Y.L., Garske, K.M., Wang, J., Firulli, B.A., Firulli, A.B., Poss, K.D., Yelon, D.
ID
ZDB-PUB-140720-3
Date
2014
Source
Development (Cambridge, England)   141(16): 3112-22 (Journal)
Registered Authors
Garske, Kristina, Poss, Kenneth D., Wang, Jinhu, Yelon, Deborah
Keywords
none
MeSH Terms
  • In Situ Hybridization
  • Sequence Homology, Amino Acid
  • In Situ Hybridization, Fluorescence
  • Gene Expression Regulation, Developmental*
  • Animals
  • Gene Expression Profiling
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
  • DNA/chemistry
  • Heart/embryology*
  • Myocytes, Cardiac/cytology*
  • Genotype
  • Zebrafish/embryology*
  • Regeneration
  • Transgenes
  • Molecular Sequence Data
  • Mice
  • Basic Helix-Loop-Helix Transcription Factors/genetics
  • Basic Helix-Loop-Helix Transcription Factors/physiology*
  • Amino Acid Sequence
  • Cell Proliferation
(all 21)
PubMed
25038045 Full text @ Development
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.
Genes / Markers
Figures
Figure Gallery (15 images) / 2
Show all Figures
Expression
Phenotype
Fish Conditions Stage Phenotype Figure
sd28Tgheat shockPrim-25
sd28Tgheat shockPrim-25
sd28Tgheat shockPrim-25
sd29Tgheat shockPrim-25
sd29Tgheat shockPrim-25
1 - 5 of 5
Show
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
f2TgTransgenic Insertion
    fb7TgTransgenic Insertion
      pd10TgTransgenic Insertion
        pd24TgTransgenic Insertion
          pd36TgTransgenic Insertion
            pd38TgTransgenic Insertion
              s6
                		Deficiency
                sd28TgTransgenic Insertion
                  sd29TgTransgenic Insertion
                    sd30TgTransgenic Insertion
                      1 - 10 of 11
                      Show
                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      No data available
                      Fish
                      Fish
                      Df(Chr01:hand2)s6/s6
                      f2Tg
                      fb7Tg
                      fb7Tg; sd28Tg
                      pd10Tg/+; pd36Tg/+
                      pd24Tg
                      pd38Tg
                      sd28Tg
                      sd29Tg
                      sd30Tg
                      1 - 10 of 12
                      Show
                      Antibodies
                      Orthology
                      Gene Orthology
                      hand2
                      1 - 1 of 1
                      Show
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      CreEFGCre
                      DipToxEFGDipTox
                      DsRedEFGDsRed
                      DsRed2EFGDsRed2
                      EGFPEFGEGFP
                      grcfpEFGgrcfp
                      mCherryEFGmCherry
                      ZsYellowEFGZsYellow
                      1 - 8 of 8
                      Show
                      Mapping
                      No data available
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                      Citation
                      Schindler, Y.L., Garske, K.M., Wang, J., Firulli, B.A., Firulli, A.B., Poss, K.D., Yelon, D. (2014) Hand2 elevates cardiomyocyte production during zebrafish heart development and regeneration. Development (Cambridge, England). 141(16):3112-22.