Loss of both GATA4 and GATA6 blocks cardiac myocyte differentiation and results in acardia in mice.
Despite significant advances in identifying signaling molecules that induce cardiogenesis in mammals, the transcription factors that control the onset of cardiac myocyte gene expression have remained elusive. Candidates include the zinc finger transcription factors GATA binding proteins 4 and 6 (GATA4, GATA6). The individual loss of either protein in mice results in lethality prior to the onset of heart development due to defects in the extra-embryonic endoderm; however, when this extra-embryonic deficiency is circumvented using tetraploid embryo complementation, cardiac myocyte differentiation initiates normally. Here we show that these factors have redundant roles in controlling the onset of cardiac myocyte differentiation. As a consequence, Gata4(-/-)Gata6(-/-) embryos completely lack hearts, although second heart field progenitor cells are still generated. Our data support a model whereby GATA4 or GATA6 are essential for expression of the network of transcription factors that regulate the onset of cardiac myocyte gene expression during mammalian development.
Zhao
Roong
R
Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, USA.
Watt
Alistair J
AJ
Battle
Michele A
MA
Li
Jixuan
J
Bondow
Benjamin J
BJ
Duncan
Stephen A
SA
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D004707:Endoderm / Q000502:physiology; D050991:GATA4 Transcription Factor / Q000172:deficiency / Q000378:metabolism*; D050993:GATA6 Transcription Factor / Q000172:deficiency / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006321:Heart / Q000196:embryology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D009841:Oligonucleotides; D020133:Reverse Transcriptase Polymerase Chain Reaction
D050991:GATA4 Transcription Factor; D050993:GATA6 Transcription Factor; C484171:Gata4 protein, mouse; C494760:Gata6 protein, mouse; D009841:Oligonucleotides