Proper coronary vascular development and heart morphogenesis depend on interaction of GATA-4 with FOG cofactors
- John D. Crispino1,5,
- Maya B. Lodish1,
- Beth L. Thurberg2,
- Silvio H. Litovsky3,
- Tucker Collins2,
- Jeffery D. Molkentin4, and
- Stuart H. Orkin1,6
- 1Division of Hematology and Oncology, Children's Hospital and Dana Farber Cancer Center, Department of Pediatrics, and Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA; 2Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA; 3Department of Pathology, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA; 4University of Cincinnati Children's Hospital, Cincinnati, Ohio 45229, USA.
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-4knock-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. Gata4 ki/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.
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Footnotes
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↵5 Present address: Ben May Institute for Cancer Research, University of Chicago, Chicago, Illinois 60637, USA.
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↵6 Corresponding author.
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E-MAIL orkin{at}rascal.med.harvard.edu; FAX (617) 355-7262.
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Article and publication are at www.genesdev.org/cgi/doi/10.1101/gad.875201.
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- Received December 19, 2000.
- Accepted February 2, 2001.
- Cold Spring Harbor Laboratory Press
