title: Nkx2-5 represses Gata1 gene expression and modulates the cellular fate of cardiac progenitors during embryogenesis.
abstract: BACKGROUND
  Recent studies suggest that the hematopoietic and cardiac lineages have close ontogenic origins, and that an early mesodermal cell population has the potential to differentiate into both lineages. Studies also suggest that specification of these lineages is inversely regulated. However, the transcriptional networks that govern the cell fate specification of these progenitors are incompletely defined.
  
  
  RESULTS
  Here, we show that Nkx2-5 regulates the hematopoietic/erythroid fate of the mesoderm precursors early during cardiac morphogenesis. Using transgenic technologies to isolate Nkx2-5 expressing cells, we observed an induction of the erythroid molecular program, including Gata1, in the Nkx2-5-null embryos. We further observed that overexpression of Nkx2-5 with an Nkx2-5-inducible embryonic stem cell system significantly repressed Gata1 gene expression and suppressed the hematopoietic/erythroid potential, but not the endothelial potential, of the embryonic stem cells. This suppression was cell-autonomous, and was partially rescued by overexpressing Gata1. In addition, we demonstrated that Nkx2-5 binds to the Gata1 gene enhancer and represses the transcriptional activity of the Gata1 gene.
  
  
  CONCLUSIONS
  Our results demonstrate that the hematopoietic/erythroid cell fate is suppressed via Nkx2-5 during mesodermal fate determination, and that the Gata1 gene is one of the targets that are suppressed by Nkx2-5.
authors.affiliation: Center for Developmental Biology, University of Texas Southwestern Medical Center, Dallas, USA.
authors.forename: Arianna
authors.initials: A
authors.lastname: Caprioli
authors.forename: Naoko
authors.initials: N
authors.lastname: Koyano-Nakagawa
authors.forename: Michelina
authors.initials: M
authors.lastname: Iacovino
authors.forename: Xiaozhong
authors.initials: X
authors.lastname: Shi
authors.forename: Anwarul
authors.initials: A
authors.lastname: Ferdous
authors.forename: Richard P
authors.initials: RP
authors.lastname: Harvey
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
authors.forename: Michael
authors.initials: M
authors.lastname: Kyba
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Garry
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics*; D047108:Embryonic Development / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000502:physiology*; D050982:GATA1 Transcription Factor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D020014:K562 Cells; D051379:Mice; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C484469:Nkx2-5 protein, mouse; D014157:Transcription Factors