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Analysis of the IKKβ/NF‐κB signaling pathway during embryonic angiogenesis
Author(s) -
Hou Yanjun,
Li Fu,
Karin Michael,
Ostrowski Michael C.
Publication year - 2008
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.21723
Subject(s) - biology , angiogenesis , microbiology and biotechnology , iκb kinase , embryonic stem cell , signal transduction , vascular endothelial growth factor a , nf κb , apoptosis , cancer research , vascular endothelial growth factor , immunology , genetics , vegf receptors , gene
The nuclear factor‐κB (NF‐κB) signaling pathway regulates cellular growth, survival, differentiation and development. In this study, the functions of IκB kinase (IKK)β in angiogenesis during mouse development were examined. Conditional disruption of the Ikkβ 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 Ikkβ 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 IKKβ/NF‐κB 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. Developmental Dynamics 237:2926–2935, 2008. © 2008 Wiley‐Liss, Inc.