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In vivo monitoring of cardiomyocyte proliferation to identify chemical modifiers of heart regeneration.

Publication ,  Journal Article
Choi, W-Y; Gemberling, M; Wang, J; Holdway, JE; Shen, M-C; Karlstrom, RO; Poss, KD
Published in: Development
February 1, 2013

Adult mammalian cardiomyocytes have little capacity to proliferate in response to injury, a deficiency that underlies the poor regenerative ability of human hearts after myocardial infarction. By contrast, zebrafish regenerate heart muscle after trauma by inducing proliferation of spared cardiomyocytes, providing a model for identifying manipulations that block or enhance these events. Although direct genetic or chemical screens of heart regeneration in adult zebrafish present several challenges, zebrafish embryos are ideal for high-throughput screening. Here, to visualize cardiomyocyte proliferation events in live zebrafish embryos, we generated transgenic zebrafish lines that employ fluorescent ubiquitylation-based cell cycle indicator (FUCCI) technology. We then performed a chemical screen and identified several small molecules that increase or reduce cardiomyocyte proliferation during heart development. These compounds act via Hedgehog, Insulin-like growth factor or Transforming growth factor β signaling pathways. Direct examination of heart regeneration after mechanical or genetic ablation injuries indicated that these pathways are activated in regenerating cardiomyocytes and that they can be pharmacologically manipulated to inhibit or enhance cardiomyocyte proliferation during adult heart regeneration. Our findings describe a new screening system that identifies molecules and pathways with the potential to modify heart regeneration.

Duke Scholars

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Published In

Development

DOI

EISSN

1477-9129

Publication Date

February 1, 2013

Volume

140

Issue

3

Start / End Page

660 / 666

Location

England

Related Subject Headings

  • Zebrafish
  • Ubiquitination
  • Transgenes
  • Transforming Growth Factor beta
  • Thiophenes
  • Signal Transduction
  • Regeneration
  • Recombinant Fusion Proteins
  • Myocytes, Cardiac
  • Male
 

Citation

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Choi, W.-Y., Gemberling, M., Wang, J., Holdway, J. E., Shen, M.-C., Karlstrom, R. O., & Poss, K. D. (2013). In vivo monitoring of cardiomyocyte proliferation to identify chemical modifiers of heart regeneration. Development, 140(3), 660–666. https://doi.org/10.1242/dev.088526
Choi, Wen-Yee, Matthew Gemberling, Jinhu Wang, Jennifer E. Holdway, Meng-Chieh Shen, Rolf O. Karlstrom, and Kenneth D. Poss. “In vivo monitoring of cardiomyocyte proliferation to identify chemical modifiers of heart regeneration.Development 140, no. 3 (February 1, 2013): 660–66. https://doi.org/10.1242/dev.088526.
Choi W-Y, Gemberling M, Wang J, Holdway JE, Shen M-C, Karlstrom RO, et al. In vivo monitoring of cardiomyocyte proliferation to identify chemical modifiers of heart regeneration. Development. 2013 Feb 1;140(3):660–6.
Choi, Wen-Yee, et al. “In vivo monitoring of cardiomyocyte proliferation to identify chemical modifiers of heart regeneration.Development, vol. 140, no. 3, Feb. 2013, pp. 660–66. Pubmed, doi:10.1242/dev.088526.
Choi W-Y, Gemberling M, Wang J, Holdway JE, Shen M-C, Karlstrom RO, Poss KD. In vivo monitoring of cardiomyocyte proliferation to identify chemical modifiers of heart regeneration. Development. 2013 Feb 1;140(3):660–666.
Journal cover image

Published In

Development

DOI

EISSN

1477-9129

Publication Date

February 1, 2013

Volume

140

Issue

3

Start / End Page

660 / 666

Location

England

Related Subject Headings

  • Zebrafish
  • Ubiquitination
  • Transgenes
  • Transforming Growth Factor beta
  • Thiophenes
  • Signal Transduction
  • Regeneration
  • Recombinant Fusion Proteins
  • Myocytes, Cardiac
  • Male