Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis

Jeffery D. Molkentin, Qing Lin, Stephen A. Duncan, Eric N. Olson

Research output: Contribution to journalArticle

857 Citations (Scopus)

Abstract

The zinc finger transcription factor GATA4 has been implicated in heart development based on its early expression in precardiogenic splanchnic mesoderm and its ability to activate the expression of a number of cardiac- specific genes. To determine the role of GATA4 in embryogenesis, we generated mice homozygous for a GATA4 null allele. Homozygous GATA4 null mice arrested in development between E7.0 and E9.5 because of severe developmental abnormalities. Mutant embryos most notably lacked a primitive heart tube and foregut and developed partially outside the yolk sac. In the mutants, the two bilaterally symmetric promyocardial primordia failed to migrate ventrally but instead remained lateral and generated two independent heart tubes that contained differentiated cardiomyocytes. We show that these deformities resulted from a general loss in lateral to ventral folding throughout the embryo. GATA4 is most highly expressed within the precardiogenic splanchnic mesoderm at the posterior lip of the anterior intestinal portal, corresponding to the region of the embryo that undergoes ventral fusion. We propose that GATA4 is required for the migration or folding morphogenesis of the precardiogenic splanchnic mesodermal cells at the level of the AlP.

Original languageEnglish (US)
Pages (from-to)1061-1072
Number of pages12
JournalGenes and Development
Volume11
Issue number8
StatePublished - Apr 15 1997

Fingerprint

GATA4 Transcription Factor
Viscera
Morphogenesis
Embryonic Structures
Mesoderm
Yolk Sac
Zinc Fingers
Lip
Cardiac Myocytes
Embryonic Development
Alleles
Genes

Keywords

  • anterior intestinal portal
  • cardia bifida
  • cardiac morphogenesis
  • foregut
  • GATA4
  • transcription

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis. / Molkentin, Jeffery D.; Lin, Qing; Duncan, Stephen A.; Olson, Eric N.

In: Genes and Development, Vol. 11, No. 8, 15.04.1997, p. 1061-1072.

Research output: Contribution to journalArticle

Molkentin, Jeffery D. ; Lin, Qing ; Duncan, Stephen A. ; Olson, Eric N. / Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis. In: Genes and Development. 1997 ; Vol. 11, No. 8. pp. 1061-1072.
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