Poster abstracts

Poster number 48 submitted by Sankha Ghosh

Synergistic Effect of Ets1 and Ets2 in Regulation of Angiogenesis

Sankha Ghosh (Molecular and Cellular Biochemistry, Molecular Cellular and Developmental Biology, The Ohio State University), Ruchika Srinivasan (Molecular and Cellular Biochemistry, Molecular Cellular and Developmental Biology, The Ohio State University), Michael C Ostrowski (Molecular and Cellular Biochemistry, Comprehensive Cancer Center, Molecular Cellular and Developmental Biology, The Ohio State University)

Abstract:
Angiogenesis is the formation of new blood vessels from pre-existing vasculature. It requires an intricate cross talk between various cellular events including survival, proliferation, directed cell migration and tubular morphogenesis of endothelial cells (ECs). An extensive literature implicates the transcription factors Ets1 and Ets2 as essential elements of this complex network. Mutation of both Ets1 and Ets2 results in embryonic lethality at mid-gestation with a striking reduction in vascular branching. In vitro assays with isolated aortic ECs reveal involvement of Ets1 and Ets2 in directly regulating anti-apoptotic genes with a concomitant increase in EC apoptosis both in vivo and in vitro. These results indicate that Ets1 and Ets2 play essential and synergistic roles in coordinating EC survival during embryonic angiogenesis. However the precise mechanism through which these pathways integrate to orchestrate other EC autonomous functions required for angiogenesis in vivo remains ill defined. The aim of this study is to decipher the mechanistic details of the coordinated Ets1 and Ets2 pathways and delineate the synergistic effects of Ets1/2 in maintaining different cellular events involved in angiogenesis.
In the absence of Ets1 and Ets2, several cellular functions were significantly impaired. In addition to increased apoptosis levels, a surprisingly large population of DKO cells were found present in the G2/M phase of the cell cycle. This result may indicate that induction of apoptosis may only be a secondary effect of a cell cycle arrest at G2/M phase. The DKO cells were significantly less proliferative and less adherent compared to the control cells. The deletion of Ets1/2 also resulted in defective tube formation by the DKO ECs. The retinas of 7 day old mice exhibited considerably attenuated angiogenesis when Ets1 and Ets2 were conditionally knocked out in EC with a tamoxifen inducible cre in new born (P1-3) mice. Taken together, these findings strongly suggest that both genes are instrumental in coordinating various EC functions leading to angiogenesis.

Keywords: Angiogeneis, Endothelial Cells