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Published online 11 December 2006. doi:10.1083/jcb.200605149
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 175, Number 6, 981-991
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Article

 JunB is required for endothelial cell morphogenesis by regulating core-binding factor ß

Alexander H. Licht1, Oliver T. Pein1, Lore Florin1, Bettina Hartenstein1, Hendrik Reuter2, Bernd Arnold3, Peter Lichter2, Peter Angel1, and Marina Schorpp-Kistner1

1 Division of Signal Transduction and Growth Control, 2 Division of Molecular Genetics, and 3 Division of Molecular Immunology, German Cancer Research Center (Deutsches Krebsforschungszentrum), D-69120 Heidelberg, Germany

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.

A.H. Licht and O.T. Pein contributed equally to this paper.

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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