Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis. Genes Dev 1997 Apr 15;11(8):1061-72
Date
04/15/1997Pubmed ID
9136933DOI
10.1101/gad.11.8.1061Scopus ID
2-s2.0-0030996908 (requires institutional sign-in at Scopus site) 991 CitationsAbstract
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 AIP.
Author List
Molkentin JD, Lin Q, Duncan SA, Olson ENMESH terms used to index this publication - Major topics in bold
AnimalsBody Patterning
DNA-Binding Proteins
Digestive System
Embryonic and Fetal Development
GATA4 Transcription Factor
GATA5 Transcription Factor
GATA6 Transcription Factor
Gastrula
Gene Expression Regulation, Developmental
Heart
Mice
Mice, Mutant Strains
Morphogenesis
Myocardium
Nervous System
RNA, Messenger
Transcription Factors
Yolk Sac