Document Detail

Regulation of vasculogenesis and angiogenesis by EphB/ephrin-B2 signaling between endothelial cells and surrounding mesenchymal cells.
MedLine Citation:
PMID:  12149214     Owner:  NLM     Status:  MEDLINE    
Although the cellular and molecular mechanisms governing angiogenesis are only beginning to be understood, signaling through endothelial-restricted receptors, particularly receptor tyrosine kinases, has been shown to play a pivotal role in these events. Recent reports show that EphB receptor tyrosine kinases and their transmembrane-type ephrin-B2 ligands play essential roles in the embryonic vasculature. These studies suggest that cell-to-cell repellent effects due to bidirectional EphB/ephrin-B2 signaling may be crucial for vascular development, similar to the mechanism described for neuronal development. To test this hypothesis, we disrupted the precise expression pattern of EphB/ephrin-B2 in vivo by generating transgenic (CAGp-ephrin-B2 Tg) mice that express ephrin-B2 under the control of a ubiquitous and constitutive promoter, CMV enhancer-beta-actin promoter-beta-globin splicing acceptor (CAG). These mice displayed an abnormal segmental arrangement of intersomitic vessels, while such anomalies were not observed in Tie-2p-ephrin-B2 Tg mice in which ephrin-B2 was overexpressed in only vascular endothelial cells (ECs). This finding suggests that non-ECs expressing ephrin-B2 alter the migration of ECs expressing EphB receptors into the intersomitic region where ephrin-B2 expression is normally absent. CAGp-ephrin-B2 Tg mice show sudden death at neonatal stages from aortic dissecting aneurysms due to defective recruitment of vascular smooth muscle cells to the ascending aorta. EphB/ephrin-B2 signaling between endothelial cells and surrounding mesenchymal cells plays an essential role in vasculogenesis, angiogenesis, and vessel maturation.
Yuichi Oike; Yasuhiro Ito; Koichi Hamada; Xiu-Qin Zhang; Keishi Miyata; Fumio Arai; Tomohisa Inada; Kimi Araki; Naomi Nakagata; Motohiro Takeya; Yaz Y Kisanuki; Masashi Yanagisawa; Nicholas W Gale; Toshio Suda
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Blood     Volume:  100     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2002 Aug 
Date Detail:
Created Date:  2002-07-31     Completed Date:  2002-09-12     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1326-33     Citation Subset:  AIM; IM    
Department of Cell Differentiation, the Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
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MeSH Terms
Actins / genetics
Aneurysm, Dissecting / genetics
Animals, Newborn
Aortic Aneurysm / genetics
Blood Vessels / embryology*
Capillaries / metabolism
Cell Line
Cytomegalovirus / genetics
Endothelium, Vascular / metabolism*
Enhancer Elements, Genetic
Gene Expression
Globins / genetics
Membrane Proteins / genetics,  physiology*
Mesoderm / metabolism*
Mice, Transgenic
Muscle, Smooth, Vascular / metabolism
Neovascularization, Physiologic / physiology*
Promoter Regions, Genetic
RNA Splicing
Receptor Protein-Tyrosine Kinases / physiology
Receptors, Eph Family
Signal Transduction*
Reg. No./Substance:
0/Actins; 0/Ephrin-B2; 0/Membrane Proteins; 9004-22-2/Globins; EC Protein-Tyrosine Kinases; EC, Eph Family

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