Hand2 elevates cardiomyocyte production during zebrafish heart development and regeneration

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

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3112-3122
Number of pages11
JournalDevelopment (Cambridge)
Volume141
Issue number16
DOIs
StatePublished - 2014

Fingerprint

Zebrafish
Cardiac Myocytes
Regeneration
Basic Helix-Loop-Helix Transcription Factors
Regenerative Medicine
Wounds and Injuries
Cardiomegaly
Mesoderm
Blood Vessels
Heart Diseases
Embryonic Structures
DNA

Keywords

  • Cardiac regeneration
  • First heart field
  • Hand2
  • Second heart field
  • Zebrafish

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

Cite this

Schindler, Y. L., Garske, K. M., Wang, J., Firulli, B. A., Firulli, A., Poss, K. D., & Yelon, D. (2014). Hand2 elevates cardiomyocyte production during zebrafish heart development and regeneration. Development (Cambridge), 141(16), 3112-3122. https://doi.org/10.1242/dev.106336

Hand2 elevates cardiomyocyte production during zebrafish heart development and regeneration. / Schindler, Yocheved L.; Garske, Kristina M.; Wang, Jinhu; Firulli, Beth A.; Firulli, Anthony; Poss, Kenneth D.; Yelon, Deborah.

In: Development (Cambridge), Vol. 141, No. 16, 2014, p. 3112-3122.

Research output: Contribution to journalArticle

Schindler, YL, Garske, KM, Wang, J, Firulli, BA, Firulli, A, Poss, KD & Yelon, D 2014, 'Hand2 elevates cardiomyocyte production during zebrafish heart development and regeneration', Development (Cambridge), vol. 141, no. 16, pp. 3112-3122. https://doi.org/10.1242/dev.106336
Schindler, Yocheved L. ; Garske, Kristina M. ; Wang, Jinhu ; Firulli, Beth A. ; Firulli, Anthony ; Poss, Kenneth D. ; Yelon, Deborah. / Hand2 elevates cardiomyocyte production during zebrafish heart development and regeneration. In: Development (Cambridge). 2014 ; Vol. 141, No. 16. pp. 3112-3122.
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