期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：24
页码：14030-14035
DOI：10.1073/pnas.1936250100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：GATA transcription factors, together with Friend of GATA (FOG) cofactors, are required for the differentiation of diverse cell types. Multiple aspects of hematopoiesis are controlled by the interaction of FOG-1 with the GATA-1/2/3 subfamily. Likewise, FOG-2 is coexpressed with the GATA-4/5/6 subfamily at other sites, including the heart and gonads. FOG-2 and GATA-4 are required for cardiac development. Through transgenic rescue of hematopoietic defects of FOG-1-/- embryos we define an unsuspected role for FOG-1 in heart development. In particular, rescued FOG-1-/- mice die at embryonic day (E) 14.5 with cardiac defects that include double outlet right ventricle and a common atrioventricular valve. Using conditional inactivation of Fog-1 we assign the cell of origin in which FOG-1 function is required. Neural crest cells migrate properly into FOG-1-/- hearts and mice with FOG-1 conditionally excised from neural crest derivatives fail to develop cardiac abnormalities. In contrast, conditional inactivation of FOG-1 in endothelial-derived tissues by means of Tie-2-expressed Cre recapitulates the rescue-knockout defects. These findings establish a nonredundant requirement for FOG-1 in the outlet tract and atrioventricular valves of the heart that depend on expression in endothelial-derived tissue and presumably reflect cooperation with the GATA-4/5/6 subfamily.
