Abstract 174: Lacking Gata2 in Endothelial Cells Induces Apoptosis During Vascular Development
Gata2 is a transcription factor implicated in hematopoietic development. Previously, we utilized zinc-finger nucleases to generate a zebrafish mutant in gata2a, which reveals a novel role for this gene in vascular development. In particular, gata2a mutant embryos exhibit defects in blood flow circulation due to the formation of shunts within trunk blood vessels, although artery and vein identity appears normal. Here, we show that endothelial cells in gata2a mutant embryos specifically undergo apoptosis as revealed by positive staining of activated caspase-3 at 30hpf but not 24hpf. This endothelial apoptosis can be rescued by re-constitution of gata2a or overexpression of a well-known anti-apoptotic protein, bcl2l1. Interestingly, knocking-down p53 has no effect on the rescue of apoptosis in gata2a mutants, suggesting a p53 independent pathway of apoptosis. Furthermore, we find that mouse retinal vascular endothelial cells lacking gata2 also appear to undergo apoptosis, which prevent angiogenic sprouting from the superficial to media layer of retina vasculature. These findings reveal a new role of gata2 in vascular development whereby gata2 retains an anti-apoptotic function in endothelial cells.
Author Disclosures: C. Ni: None. T. Smith: None. N.D. Lawson: None.
- © 2014 by American Heart Association, Inc.