Nkx2.5 marks angioblasts that contribute to hemogenic endothelium of the endocardium and dorsal aorta

Elife. 2017 Mar 8;6:e20994. doi: 10.7554/eLife.20994.

Abstract

Novel regenerative therapies may stem from deeper understanding of the mechanisms governing cardiovascular lineage diversification. Using enhancer mapping and live imaging in avian embryos, and genetic lineage tracing in mice, we investigated the spatio-temporal dynamics of cardiovascular progenitor populations. We show that expression of the cardiac transcription factor Nkx2.5 marks a mesodermal population outside of the cardiac crescent in the extraembryonic and lateral plate mesoderm, with characteristics of hemogenic angioblasts. Extra-cardiac Nkx2.5 lineage progenitors migrate into the embryo and contribute to clusters of CD41+/CD45+ and RUNX1+ cells in the endocardium, the aorta-gonad-mesonephros region of the dorsal aorta and liver. We also demonstrated that ectopic expression of Nkx2.5 in chick embryos activates the hemoangiogenic gene expression program. Taken together, we identified a hemogenic angioblast cell lineage characterized by transient Nkx2.5 expression that contributes to hemogenic endothelium and endocardium, suggesting a novel role for Nkx2.5 in hemoangiogenic lineage specification and diversification.

Keywords: Nkx2.5; cardiogenesis; developmental biology; hemangioblasts; hemogenic endothelium; nkx2.5; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / embryology*
  • Chick Embryo
  • Endocardium / embryology*
  • Hemangioblasts / physiology*
  • Homeobox Protein Nkx-2.5 / metabolism*
  • Mice
  • Spatio-Temporal Analysis

Substances

  • Homeobox Protein Nkx-2.5
  • Nkx2-5 protein, mouse

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.