PUBLICATION

Tbx20 Is an Essential Regulator of Embryonic Heart Growth in Zebrafish

Authors
Just, S., Raphel, L., Berger, I.M., Bühler, A., Keßler, M., Rottbauer, W.
ID
ZDB-PUB-161203-6
Date
2016
Source
PLoS One   11: e0167306 (Journal)
Registered Authors
Berger, Ina, Bühler, Anja, Just, Steffen, Keßler, Mirjam, Raphel, Linda, Rottbauer, Wolfgang
Keywords
Zebrafish, Embryos, Heart, Hyperexpression techniques, Cardiac ventricles, Transcription factors, DNA sequence analysis, BAC cloning
MeSH Terms
  • Cell Proliferation
  • Mutation
  • Gene Expression Regulation, Developmental*
  • Phenotype
  • Gene Knockdown Techniques
  • Animals
  • Heart/embryology*
  • T-Box Domain Proteins/genetics*
  • Myocytes, Cardiac/metabolism
  • Zebrafish Proteins/genetics*
  • Zebrafish/genetics
  • Organogenesis/genetics*
  • Ectopic Gene Expression
(all 13)
PubMed
27907103 Full text @ PLoS One
Abstract
The molecular mechanisms that regulate cardiomyocyte proliferation during embryonic heart growth are not completely deciphered yet. In a forward genetic N-ethyl-N-nitrosourea (ENU) mutagenesis screen, we identified the recessive embryonic-lethal zebrafish mutant line weiches herz (whz). Homozygous mutant whz embryos display impaired heart growth due to diminished embryonic cardiomyocyte proliferation resulting in cardiac hypoplasia and weak cardiac contraction. By positional cloning, we found in whz mutant zebrafish a missense mutation within the T-box 20 (Tbx20) transcription factor gene leading to destabilization of Tbx20 protein. Morpholino-mediated knock-down of Tbx20 in wild-type zebrafish embryos phenocopies whz, indicating that the whz phenotype is due to loss of Tbx20 function, thereby leading to significantly reduced cardiomyocyte numbers by impaired proliferation of heart muscle cells. Ectopic overexpression of wild-type Tbx20 in whz mutant embryos restored cardiomyocyte proliferation and heart growth. Interestingly, ectopic overexpression of Tbx20 in wild-type zebrafish embryos resulted, similar to the situation in the embryonic mouse heart, in significantly reduced proliferation rates of ventricular cardiomyocytes, suggesting that Tbx20 activity needs to be tightly fine-tuned to guarantee regular cardiomyocyte proliferation and embryonic heart growth in vivo.
Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
m245
    Point Mutation
    s883TgTransgenic Insertion
      1 - 2 of 2
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      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      Target Reagent Reagent Type
      tbx20MO3-tbx20MRPHLNO
      tbx20MO4-tbx20MRPHLNO
      1 - 2 of 2
      Show
      Fish
      Antibodies
      Orthology
      No data available
      Engineered Foreign Genes
      Marker Marker Type Name
      EGFPEFGEGFP
      1 - 1 of 1
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      Mapping
      No data available