Analysis of the IKKbeta/NF-kappaB signaling pathway during embryonic angiogenesis.

The nuclear factor-kappaB (NF-kappaB) signaling pathway regulates cellular growth, survival, differentiation and development. In this study, the functions of IkappaB kinase (IKK)beta in angiogenesis during mouse development were examined. Conditional disruption of the Ikkbeta locus in endothelial cells using the well-characterized Tie2-Cre transgene resulted in embryonic lethality between embryonic day (E) 13.5 and E15.5. Examination of the mutant embryos revealed that while deletion of Ikkbeta occurred in endothelial cells throughout the embryo, only the vascular network in the fetal liver was affected. Disruption of the fetal liver vasculature was accompanied by decreased cell proliferation and increased apoptosis of hepatocytes, but hematopoiesis was not affected. Increased apoptosis was not observed outside of fetal liver in the mutant embryos. These results indicate that the IKKbeta/NF-kappaB pathway plays a previously unappreciated role in development of the sinusoidal vasculature in the fetal liver and additionally that this pathway is critical in the crosstalk between endothelial cells and hepatocytes during mouse development. Copyright (c) 2008 Wiley-Liss, Inc.