Expression of ErbB receptors in ES cell-derived cardiomyocytes

Biochem Biophys Res Commun. 2003 Sep 12;309(1):241-6. doi: 10.1016/s0006-291x(03)01521-3.

Abstract

To explore the role of ErbB-mediated signaling in cardiogenesis of ES cells, we examined the expression of ErbB receptors as well as effects of a ligand and inhibitors using Nkx2.5GFP ES cells, in which the GFP gene was knocked-in to the Nkx2.5 locus to monitor cardiac differentiation. Although all ErbB receptors were expressed in developing embryoid bodies, expression of ErbB4 was almost exclusively found in differentiated cardiomyocytes. Heregulin beta1, a ligand of ErbB receptors, enhanced the generation of Nkx2.5/GFP(+) cardiomyocytes in embryoid bodies, while AG1478 and PD153035, inhibitors of ErbBs, drastically blocked the generation of Nkx2.5/GFP(+) cardiomyocytes. These results suggest that the signaling pathway mediated by ErbBs is important in the induction and differentiation of cardiomyocytes from ES cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Differentiation
  • Cell Division
  • Culture Media, Serum-Free / pharmacology
  • Embryo, Mammalian / cytology*
  • Enzyme Inhibitors / pharmacology
  • ErbB Receptors / biosynthesis*
  • Green Fluorescent Proteins
  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins / metabolism
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Ligands
  • Luminescent Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Microscopy, Fluorescence
  • Myocardium / cytology*
  • Neuregulin-1 / metabolism
  • Quinazolines / pharmacology
  • Receptor, ErbB-4
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Stem Cells / metabolism*
  • Time Factors
  • Transcription Factors*
  • Tyrphostins / pharmacology
  • Xenopus Proteins / metabolism

Substances

  • Culture Media, Serum-Free
  • Enzyme Inhibitors
  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins
  • Ligands
  • Luminescent Proteins
  • NKX2-5 protein, human
  • Neuregulin-1
  • Nkx2-5 protein, mouse
  • Quinazolines
  • Transcription Factors
  • Tyrphostins
  • Xenopus Proteins
  • Green Fluorescent Proteins
  • heregulin beta1
  • RTKI cpd
  • ERBB4 protein, human
  • ErbB Receptors
  • Erbb4 protein, mouse
  • Receptor, ErbB-4
  • 4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline