Nkx2-5 represses gata1 gene expression and modulates the cellular fate of cardiac progenitors during embryogenesis

Arianna Caprioli, Naoko Koyano-Nakagawa, Michelina Iacovino, Xiaozhong Shi, Anwarul Ferdous, Richard P. Harvey, Eric N. Olson, Michael Kyba, Daniel J. Garry

Research output: Contribution to journalArticle

36 Scopus citations

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. Methods and 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.

Original languageEnglish (US)
Pages (from-to)1633-1641
Number of pages9
JournalCirculation
Volume123
Issue number15
DOIs
StatePublished - Apr 19 2011

Keywords

  • Nkx2-5 protein
  • developmental genes
  • gene expression regulation
  • mouse

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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