A threshold of GATA4 and GATA6 expression is required for cardiovascular development

Mei Xin, Christopher A. Davis, Jeffery D. Molkentin, Ching Ling Lien, Stephen A. Duncan, James A. Richardson, Eric N. Olson

Research output: Contribution to journalArticle

129 Scopus citations

Abstract

The zinc-finger transcription factors GATA4 and GATA6 play critical roles in embryonic development. Mouse embryos lacking GATA4 die at embryonic day (E) 8.5 because of failure of ventral foregut closure and cardiac bifida, whereas GATA6 is essential for development of the visceral endoderm. Although mice that are heterozygous for either a GATA4 or GATA6 null allele are normal, we show that compound heterozygosity of GATA4 and GATA6 results in embryonic lethality by E13.5 accompanied by a spectrum of cardiovascular defects, including thin-walled myocardium, ventricular and aortopulmonary septal defects, and abnormal smooth muscle development. Myocardial hypoplasia in GATA4/GATA6 double heterozygous mutant embryos is associated with reduced proliferation of cardiomyocytes, diminished expression of the myogenic transcription factor MEF2C (myocyte enhancer factor 2C), and down-regulation of β-myosin heavy chain expression, a key determinant of cardiac contractility. These findings reveal a threshold of GATA4 and GATA6 activity that is required for gene expression in the developing cardiovascular system and underscore the potential of recessive mutations to perturb the delicate regulation of cardiovascular development.

Original languageEnglish (US)
Pages (from-to)11189-11194
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number30
DOIs
StatePublished - Jul 25 2006

Keywords

  • Cardiogenesis
  • GATA factors
  • Heart defects
  • Heart development
  • Ventricular septal defect

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'A threshold of GATA4 and GATA6 expression is required for cardiovascular development'. Together they form a unique fingerprint.

Cite this