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    Genes Dev. 2001 Apr 1;15(7):839-44.

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

    Crispino JD, Lodish MB, Thurberg BL, Litovsky SH, Collins T, Molkentin JD, Orkin SH.

    Division of Hematology and Oncology, Children's Hospital, Boston, Massachusetts 02115, USA.

    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. 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.

    PMID: 11297508 [PubMed - indexed for MEDLINE]

    PMCID: 312667

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