Document Detail


Loss of distinct arterial and venous boundaries in mice lacking endoglin, a vascular-specific TGFbeta coreceptor.
MedLine Citation:
PMID:  12941632     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Several characteristic morphological and functional differences distinguish arteries from veins. It was thought that hemodynamic forces shaped these differences; however, increasing evidence suggests that morphogenetic programs play a central role in blood vessel differentiation. Hereditary hemorrhagic telangiectasia (HHT) is a vascular dysplasia characterized by the inappropriate fusion of arterioles with venules. The genes implicated in this disease, ALK1 and endoglin, may be involved in defining the fundamental boundaries between arteries and veins. We previously showed that mice lacking Alk1 lost structural, molecular, and functional distinctions between arteries and veins. Here, we report that mice lacking endoglin develop arterial-venous malformations and fail to confine intraembryonic hematopoiesis to arteries. In contrast to Alk1 mutants, endoglin mutants do not show profound vessel dilation or downregulation of arterial ephrinB2. Finally, our data indicate that a failure in cardiac cushion formation observed in both strains may be secondary to the peripheral vasculature defect. The phenotypic similarities, yet reduced severity, implicates endoglin as an accessory coreceptor that specifically modulates Alk1 signaling. We propose that endoglin and Alk1 are necessary for the maintenance of distinct arterial-venous vascular beds and that attenuation of the Alk1 signaling pathway is the precipitating event in the etiology of HHT.
Authors:
Lise K Sorensen; Benjamin S Brooke; Dean Y Li; Lisa D Urness
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Developmental biology     Volume:  261     ISSN:  0012-1606     ISO Abbreviation:  Dev. Biol.     Publication Date:  2003 Sep 
Date Detail:
Created Date:  2003-08-27     Completed Date:  2003-10-21     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  235-50     Citation Subset:  IM    
Affiliation:
Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Activin Receptors, Type I / deficiency,  genetics,  physiology*
Animals
Antigens, CD
Arteries / embryology
Arteriovenous Malformations / embryology,  genetics
Base Sequence
Blood Vessels / embryology*
DNA / genetics
Endocardial Cushion Defects / embryology,  genetics
Ephrin-B2 / genetics
Hematopoiesis / genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Phenotype
Receptors, Cell Surface
Receptors, Transforming Growth Factor beta / physiology*
Telangiectasia, Hereditary Hemorrhagic / embryology,  genetics
Vascular Cell Adhesion Molecule-1 / genetics,  physiology*
Veins / embryology
Grant Support
ID/Acronym/Agency:
R01 HL077671-03/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/ENG protein, human; 0/Ephrin-B2; 0/Receptors, Cell Surface; 0/Receptors, Transforming Growth Factor beta; 0/Vascular Cell Adhesion Molecule-1; 9007-49-2/DNA; EC 2.7.11.30/Activin Receptors, Type I; EC 2.7.11.30/Acvrl1 protein, mouse

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  A role for septins in cellular and axonal migration in C. elegans.
Next Document:  Robo4 is a vascular-specific receptor that inhibits endothelial migration.