| Endothelial lineage-mediated loss of the GATA cofactor Friend of GATA 1 impairs cardiac development. | |
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MedLine Citation:
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PMID: 14614148 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Samuel G Katz; Aimee Williams; Jifu Yang; Yuko Fujiwara; Alice P Tsang; Jonathan A Epstein; Stuart H Orkin |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. Date: 2003-11-12 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 100 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2003 Nov |
Date Detail:
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Created Date: 2003-12-03 Completed Date: 2004-02-02 Revised Date: 2013-04-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 14030-5 Citation Subset: IM |
Affiliation:
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Division of Hematology/Oncology, Children's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Carrier Proteins / genetics, physiology DNA-Binding Proteins / metabolism Endothelium / embryology Erythroid-Specific DNA-Binding Factors Fetal Heart / abnormalities, embryology*, metabolism GATA1 Transcription Factor Heart Defects, Congenital / embryology, genetics Heart Valves / abnormalities, embryology Hematopoiesis / genetics, physiology In Situ Hybridization Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Neural Crest / embryology Nuclear Proteins / deficiency*, genetics, physiology Transcription Factors / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Carrier Proteins; 0/DNA-Binding Proteins; 0/Erythroid-Specific DNA-Binding Factors; 0/GATA1 Transcription Factor; 0/Gata1 protein, mouse; 0/Nuclear Proteins; 0/Transcription Factors; 0/Zfpm1 protein, mouse |
| Comments/Corrections | |
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