Document Detail


Selective regulation of arterial branching morphogenesis by synectin.
MedLine Citation:
PMID:  16740480     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Branching morphogenesis is a key process in the formation of vascular networks. To date, little is known regarding the molecular events regulating this process. We investigated the involvement of synectin in this process. In zebrafish embryos, synectin knockdown resulted in a hypoplastic dorsal aorta and hypobranched, stunted, and thin intersomitic vessels due to impaired migration and proliferation of angioblasts and arterial endothelial cells while not affecting venous development. Synectin(-/-) mice demonstrated decreased body and organ size, reduced numbers of arteries, and an altered pattern of arterial branching in multiple vascular beds while the venous system remained normal. Murine synectin(-/-) primary arterial, but not venous, endothelial cells showed decreased in vitro tube formation, migration, and proliferation and impaired polarization due to abnormal localization of activated Rac1. We conclude that synectin is involved in selective regulation of arterial, but not venous, growth and branching morphogenesis and that Rac1 plays an important role in this process.
Authors:
Thomas W Chittenden; Filip Claes; Anthony A Lanahan; Monica Autiero; Robert T Palac; Eugene V Tkachenko; Arye Elfenbein; Carmen Ruiz de Almodovar; Eduard Dedkov; Robert Tomanek; Weiming Li; Michael Westmore; Jai Pal Singh; Arie Horowitz; Mary Jo Mulligan-Kehoe; Karen L Moodie; Zhen W Zhuang; Peter Carmeliet; Michael Simons
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Developmental cell     Volume:  10     ISSN:  1534-5807     ISO Abbreviation:  Dev. Cell     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-06-02     Completed Date:  2006-07-19     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  101120028     Medline TA:  Dev Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  783-95     Citation Subset:  IM    
Affiliation:
Angiogenesis Research Center, Section of Cardiology, Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arteries / abnormalities,  cytology,  embryology*,  growth & development*
Carrier Proteins / chemistry,  genetics,  metabolism
Cell Movement
Cell Proliferation
Cells, Cultured
Embryo, Nonmammalian
Endothelial Cells / cytology,  physiology
Endothelium, Vascular / cytology
Female
Femoral Artery / cytology
Gene Expression Regulation
Gene Expression Regulation, Developmental
Mice
Mice, Knockout
Morphogenesis*
Myocardium / cytology
Neuropeptides / deficiency*,  genetics
Pregnancy
Venae Cavae / cytology
Zebrafish / embryology*
Zebrafish Proteins / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
HL067960/HL/NHLBI NIH HHS; HL53793/HL/NHLBI NIH HHS; HL62289/HL/NHLBI NIH HHS; T32 AR007576/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Neuropeptides; 0/Rgs19ip1 protein, mouse; 0/Zebrafish Proteins; 0/synectin protein, zebrafish

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