Abstract 18885: Er71 Regulates Endothelial and Hematopoietic Cell Development During Embryogenesis
The endothelial and hematopoietic cell lineages are specified early during mammalian extra- and embryonic development. Within the extraembryonic yolk sac and embryo, mesodermal progenitor cells develop into a vascular plexus structure and further remodel and differentiate into vascular, hematopoietic structures. During these early extra- and embryonic developmental stages, various transcription factors such as members of the Sox, Ets, Forkhead, GATA, and other transcription factor families have been known to play an essential role in development. We hypothesize that a common progenitor (the hemangioblast) daughters both the endothelial and hematopoietic lineages and Ets related protein 71 (ER71) is a master regulator of this population. To examine this hypothesis, we generated an ER71 knockout mouse model, an ER71 promoter-EYFP expressing transgenic mouse and an inducible ES/EB model that overexpresses ER71 in mouse embryonic stem cells at distinct stages of differentiation. Using these technologies, we observed that ER71 is transiently expressed in endothelial and primitive blood cells during early extra- and embryonic development. Analysis of the ER71 null embryo reveals the lack of the hematopoietic and endothelial/endocardial lineages resulting in early lethality (E8-E9.0). We further observed an absence of primitive hematopoiesis and mature endothelial lineages within the ER71 null extraembryonic yolk sac. Moreover, forced overexpression of ER71 during embryoid body differentiation supports the notion that ER71 induces both the hematopoietic and endothelial lineages. Collectively, our studies support the hypothesis that ER71 is essential for the specification of the hemangioblast cell population early during embryogenesis.
- © 2010 by American Heart Association, Inc.