Abstract 15450: Ets Related Protein 71 Regulates Cardiac Morphogenesis
To decipher the Nkx2-5 mediated transcriptional networks that govern fate decisions in multipotent cardiac progenitor cells, a transcriptome analysis revealed that Ets related protein 71 (ER71) was a downstream target of Nkx2.5 in the developing mouse heart. We further demonstrated that ER71 was essential for development of primitive hematopoiesis, the endothelial/endocardial lineages and cardiac development resulting in early (E8.0-E9.0) embryonic lethality of the ER71 null embryo. Transcriptome analysis of the ER71 null and WT littermate embryos support the hypothesis that lineage specific gene expression associated with the hematopoietic, endothelial/endocardial and cardiovascular lineages are absent or significantly dysregulated in the ER71 null embryo. To examine whether ER71 is a novel marker of a common mesangioblast progenitor population, a 3.9 kb ER71-Cre transgenic animal was engineered and mated with the Rosa lox-stop-lox-LacZ reporter mouse model. We observed that ER71 expressing cells daughter the hematopoietic, endothelial/endocardial and a subset of the myocardial lineages early during development (E9-E11). To complement these fate mapping studies, we generated the 3.9 kb ER71-EYFP transgenic mouse model and utilized FACS analysis to define the population or populations of cells in which ER71 is expressed (E7.5-E9.5). We further crossed the ER71-EYFP reporter into the ER71 null background to determine the stage at which the development of the affected lineages is aborted. Together, these studies support the conclusion that ER71 functions in uncommitted progenitor cells to affect embryonic heart development as well as endothelial and hematopoietic lineage commitments.
- © 2010 by American Heart Association, Inc.