Recapitulation of developmental cardiogenesis governs the morphological and functional regeneration of adult newt hearts following injury

Dev Biol. 2011 Jun 1;354(1):67-76. doi: 10.1016/j.ydbio.2011.03.021. Epub 2011 Mar 30.

Abstract

Urodele amphibians, like the newt, are the "champions of regeneration" as they are able to regenerate many body parts and tissues. Previous experiments, however, have suggested that the newt heart has only a limited regeneration capacity, similar to the human heart. Using a novel, reproducible ventricular resection model, we show for the first time that adult newt hearts can fully regenerate without any evidence of scarring. This process is governed by increased proliferation and the up-regulation of cardiac transcription factors normally expressed during developmental cardiogenesis. Furthermore, we are able to identify cells within the newly regenerated regions of the myocardium that express the LIM-homeodomain protein Islet1 and GATA4, transcription factors found in cardiac progenitors. Information acquired from using the newt as a model organism may help to shed light on the regeneration deficits demonstrated in damaged human hearts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • GATA4 Transcription Factor / genetics
  • Gene Expression
  • Heart / physiopathology*
  • Heart Injuries / physiopathology*
  • Homeodomain Proteins / genetics
  • LIM-Homeodomain Proteins
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Myocardium / metabolism
  • Myocardium / pathology
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Regeneration*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Salamandridae / genetics
  • Salamandridae / physiology*
  • Transcription Factors

Substances

  • GATA4 Transcription Factor
  • Homeodomain Proteins
  • LIM-Homeodomain Proteins
  • Transcription Factors
  • insulin gene enhancer binding protein Isl-1