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JunB is required for endothelial cell morphogenesis by regulating core-binding factor ß
Correspondence to M. Schorpp-Kistner: marina.schorpp{at}dkfz.de
The molecular mechanism triggering the organization of endothelial cells (ECs) in multicellular tubules is mechanistically still poorly understood. We demonstrate that cell-autonomous endothelial functions of the AP-1 subunit JunB are required for proper endothelial morphogenesis both in vivo in mouse embryos with endothelial-specific ablation of JunB and in in vitro angiogenesis models. By cDNA microarray analysis, we identified core-binding factor ß (CBFß), which together with the Runx proteins forms the heterodimeric core-binding transcription complex CBF, as a novel JunB target gene. In line with our findings, expression of the CBF target MMP-13 was impaired in JunB-deficient ECs. Reintroduction of CBFß into JunB-deficient ECs rescued the tube formation defect and MMP-13 expression, indicating an important role for CBFß in EC morphogenesis.
Abbreviations used in this paper: AP-1, activator protein-1; CBF, core-binding factor; ChIP, chromatin immunoprecipitation; CRE, cAMP responsive element; E, embryonic day; EC, endothelial cell; MMP, matrix metalloproteinase; TRE, 12-O-tetradecanoylphorbol-13-acetate–responsive element.
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