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

Alexander H Licht; Oliver T Pein; Lore Florin; Bettina Hartenstein; Hendrik Reuter; Bernd Arnold; Peter Lichter; Peter Angel; Marina Schorpp-Kistner

doi:10.1083/jcb.200605149

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

J Cell Biol. 2006 Dec 18;175(6):981-91. doi: 10.1083/jcb.200605149. Epub 2006 Dec 11.

Authors

Alexander H Licht¹, Oliver T Pein, Lore Florin, Bettina Hartenstein, Hendrik Reuter, Bernd Arnold, Peter Lichter, Peter Angel, Marina Schorpp-Kistner

Affiliation

¹ Division of Signal Transduction and Growth Control, German Cancer Research Center, Deutsches Krebsforschungszentrum, D-69120 Heidelberg, Germany.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Aorta / cytology
Aorta / metabolism
Blotting, Western
Cell Hypoxia
Cell Movement
Cells, Cultured
Chromatin Immunoprecipitation
Collagen Type II / genetics
Collagen Type II / physiology
Core Binding Factor alpha Subunits / metabolism
Core Binding Factor beta Subunit / genetics
Core Binding Factor beta Subunit / metabolism*
Endothelium, Vascular / cytology*
Endothelium, Vascular / metabolism
Fluorescent Antibody Technique
Integrases / metabolism
Lung / cytology
Lung / metabolism
Matrix Metalloproteinase 13 / genetics
Matrix Metalloproteinase 13 / physiology
Mice
Mice, Transgenic
Morphogenesis*
Neoplasm Invasiveness
Neovascularization, Pathologic
Oligonucleotide Array Sequence Analysis
Polymerase Chain Reaction
Promoter Regions, Genetic
Proto-Oncogene Proteins c-jun / genetics
Proto-Oncogene Proteins c-jun / physiology*
Transcription, Genetic

Substances

Collagen Type II
Core Binding Factor alpha Subunits
Core Binding Factor beta Subunit
Proto-Oncogene Proteins c-jun
Cre recombinase
Integrases
Matrix Metalloproteinase 13