JunB is required for endothelial cell morphogenesis by regulating core-binding factor beta.
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 beta (CBFbeta), 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 CBFbeta into JunB-deficient ECs rescued the tube formation defect and MMP-13 expression, indicating an important role for CBFbeta in EC morphogenesis.
Licht
Alexander H
AH
Division of Signal Transduction and Growth Control, German Cancer Research Center, Deutsches Krebsforschungszentrum, D-69120 Heidelberg, Germany.
Pein
Oliver T
OT
Florin
Lore
L
Hartenstein
Bettina
B
Reuter
Hendrik
H
Arnold
Bernd
B
Lichter
Peter
P
Angel
Peter
P
Schorpp-Kistner
Marina
M
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D015153:Blotting, Western; D015687:Cell Hypoxia; D002465:Cell Movement; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D024043:Collagen Type II / Q000235:genetics / Q000502:physiology; D050657:Core Binding Factor alpha Subunits / Q000378:metabolism; D050658:Core Binding Factor beta Subunit / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D019426:Integrases / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic
D024043:Collagen Type II; D050657:Core Binding Factor alpha Subunits; D050658:Core Binding Factor beta Subunit; D016755:Proto-Oncogene Proteins c-jun; C045073:Cre recombinase; D019426:Integrases; D053509:Matrix Metalloproteinase 13