Proper coronary vascular development and heart morphogenesis depend on interaction of GATA-4 with FOG cofactors

J. D. Crispino, M. B. Lodish, B. L. Thurberg, S. H. Litovsky, T. Collins, J. D. Molkentin, S. H. Orkin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

245 Scopus citations

Abstract

GATA-family transcription factors are critical to the development of diverse tissues. In particular, GATA-4 has been implicated in formation of the vertebrate heart. As the mouse Gata-4 knock-out is early embryonic lethal because of a defect in ventral morphogenesis, the in vivo function of this factor in heart development remains unresolved. To search for a requirement for Gata4 in heart development, we created mice harboring a single amino acid replacement in GATA-4 that impairs its physical interaction with its presumptive cardiac cofactor FOG-2. Gata4ki/ki mice die just after embryonic day (E) 12.5 exhibiting features in common with Fog2-/- embryos as well as additional semilunar cardiac valve defects and a double-outlet right ventricle. These findings establish an intrinsic requirement for GATA-4 in heart development. We also infer that GATA-4 function is dependent on interaction with FOG-2 and, very likely, an additional FOG protein for distinct aspects of heart formation.

Original languageEnglish (US)
Pages (from-to)839-844
Number of pages6
JournalGenes and Development
Volume15
Issue number7
DOIs
StatePublished - Apr 1 2001

Keywords

  • Coronary vasculature
  • FOG cofactor
  • GATA-4
  • Heart

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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