Comprehensive gene-expression survey identifies wif1 as a modulator of cardiomyocyte differentiation

PLoS One. 2010 Dec 13;5(12):e15504. doi: 10.1371/journal.pone.0015504.


During chicken cardiac development the proepicardium (PE) forms the epicardium (Epi), which contributes to several non-myocardial lineages within the heart. In contrast to Epi-explant cultures, PE explants can differentiate into a cardiomyocyte phenotype. By temporal microarray expression profiles of PE-explant cultures and maturing Epi cells, we identified genes specifically associated with differentiation towards either of these lineages and genes that are associated with the Epi-lineage restriction. We found a central role for Wnt signaling in the determination of the different cell lineages. Immunofluorescent staining after recombinant-protein incubation in PE-explant cultures indicated that the early upregulated Wnt inhibitory factor-1 (Wif1), stimulates cardiomyocyte differentiation in a similar manner as Wnt stimulation. Concordingly, in the mouse pluripotent embryogenic carcinoma cell line p19cl6, early and late Wif1 exposure enhances and attenuates differentiation, respectively. In ovo exposure of the HH12 chicken embryonic heart to Wif1 increases the Tbx18-positive cardiac progenitor pool. These data indicate that Wif1 enhances cardiomyogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Cell Differentiation
  • Cell Lineage
  • Chick Embryo
  • Chickens
  • Extracellular Matrix Proteins / genetics*
  • Gene Expression Profiling*
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Mice
  • Microscopy, Fluorescence / methods
  • Models, Genetic
  • Myocytes, Cardiac / cytology
  • Oligonucleotide Array Sequence Analysis
  • Pericardium / metabolism
  • T-Box Domain Proteins / metabolism
  • Time Factors


  • Adaptor Proteins, Signal Transducing
  • Extracellular Matrix Proteins
  • Intercellular Signaling Peptides and Proteins
  • T-Box Domain Proteins
  • Tbx18 protein, chicken
  • Wif1 protein, mouse