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

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 <i>Nkx2.5</i> marks a mesodermal population outside of the cardiac crescent in the extraembryonic and lateral plate mesoderm, with characteristics of hemogenic angioblasts. Extra-cardiac <i>Nkx2.5</i> 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 <i>Nkx2.5</i> in chick embryos activates the hemoangiogenic gene expression program. Taken together, we identified a hemogenic angioblast cell lineage characterized by transient <i>Nkx2.5</i> expression that contributes to hemogenic endothelium and endocardium, suggesting a novel role for <i>Nkx2.5</i> in hemoangiogenic lineage specification and diversification.