title: Endothelial lineage-mediated loss of the GATA cofactor Friend of GATA 1 impairs cardiac development.
abstract: 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.
authors: Division of Hematology/Oncology, Children's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors: Samuel G
authors: SG
authors: Katz
authors: Aimee
authors: A
authors: Williams
authors: Jifu
authors: J
authors: Yang
authors: Yuko
authors: Y
authors: Fujiwara
authors: Alice P
authors: AP
authors: Tsang
authors: Jonathan A
authors: JA
authors: Epstein
authors: Stuart H
authors: SH
authors: Orkin
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004727:Endothelium / Q000196:embryology; D050981:Erythroid-Specific DNA-Binding Factors; D005318:Fetal Heart / Q000002:abnormalities / Q000196:embryology* / Q000378:metabolism; D050982:GATA1 Transcription Factor; D006330:Heart Defects, Congenital / Q000196:embryology / Q000235:genetics; D006351:Heart Valves / Q000002:abnormalities / Q000196:embryology; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009432:Neural Crest / Q000196:embryology; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; C107310:Zfpm1 protein, mouse