Document Detail

Loss of unc45a precipitates arteriovenous shunting in the aortic arches.
MedLine Citation:
PMID:  18462713     Owner:  NLM     Status:  MEDLINE    
Aortic arch malformations are common congenital disorders that are frequently of unknown etiology. To gain insight into the factors that guide branchial aortic arch development, we examined the process by which these vessels assemble in wild type zebrafish embryos and in kurzschluss(tr12) (kus(tr12)) mutants. In wild type embryos, each branchial aortic arch first appears as an island of angioblasts in the lateral pharyngeal mesoderm, then elaborates by angiogenesis to connect to the lateral dorsal aorta and ventral aorta. In kus(tr12) mutants, angioblast formation and initial sprouting are normal, but aortic arches 5 and 6 fail to form a lumenized connection to the lateral dorsal aorta. Blood enters these blind-ending vessels from the ventral aorta, distending the arteries and precipitating fusion with an adjacent vein. This arteriovenous malformation (AVM), which shunts nearly all blood directly back to the heart, is not exclusively genetically programmed, as its formation correlates with blood flow and aortic arch enlargement. By positional cloning, we have identified a nonsense mutation in unc45a in kus(tr12) mutants. Our results are the first to ascribe a role for Unc45a, a putative myosin chaperone, in vertebrate development, and identify a novel mechanism by which an AVM can form.
Matthew J Anderson; Van N Pham; Andreas M Vogel; Brant M Weinstein; Beth L Roman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-03-26
Journal Detail:
Title:  Developmental biology     Volume:  318     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-06-02     Completed Date:  2008-06-18     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  258-67     Citation Subset:  IM    
Tumor Biology Training Program, Georgetown University Medical Center, Washington, DC 20057, USA.
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MeSH Terms
Aorta, Thoracic / embryology*,  metabolism
Arteriovenous Malformations / embryology*,  genetics,  metabolism
Branchial Region / embryology,  metabolism
Codon, Nonsense
Gene Expression Regulation, Developmental
Molecular Chaperones / genetics,  metabolism*
Zebrafish / embryology*,  metabolism
Zebrafish Proteins / genetics,  metabolism*
Grant Support
Z01 HD001011-11/HD/NICHD NIH HHS
Reg. No./Substance:
0/Codon, Nonsense; 0/Molecular Chaperones; 0/Unc45a protein, zebrafish; 0/Zebrafish Proteins

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

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