Nkx2.5 is essential for forming normal heart muscle cells and for shaping the primitive heart and its surrounding vessels into a working organ. In older embryos, cells in the inner layer of the largest blood vessel (known as the dorsal aorta) generate blood stem cells that give rise to the different types of blood cells.Ī gene called Nkx2.5 encodes a protein that controls the activity of a number of complex genetic programs and has been long studied as a key player in the development of the heart. These yolk sac vessels act as a rudimentary circulatory system, connecting to the heart and blood vessels within the embryo itself. Vessels and blood initially form in the yolk sac, a membrane that surrounds the embryo. 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.Īs an animal embryo develops, it establishes a circulatory system that includes the heart, vessels and blood. We also demonstrated that ectopic expression of Nkx2.5 in chick embryos activates the hemoangiogenic gene expression program. 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 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. 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. Novel regenerative therapies may stem from deeper understanding of the mechanisms governing cardiovascular lineage diversification.
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