Document Detail

Norrin/Frizzled4 signaling in retinal vascular development and blood brain barrier plasticity.
MedLine Citation:
PMID:  23217714     Owner:  NLM     Status:  MEDLINE    
Norrin/Frizzled4 (Fz4) signaling activates the canonical Wnt pathway to control retinal vascular development. Using genetically engineered mice, we show that precocious Norrin production leads to premature retinal vascular invasion and delayed Norrin production leads to characteristic defects in intraretinal vascular architecture. In genetic mosaics, wild-type endothelial cells (ECs) instruct neighboring Fz4(-/-) ECs to produce an architecturally normal mosaic vasculature, a cell nonautonomous effect. However, over the ensuing weeks, Fz4(-/-) ECs are selectively eliminated from the mosaic vasculature, implying the existence of a quality control program that targets defective ECs. In the adult retina and cerebellum, gain or loss of Norrin/Fz4 signaling results in a cell-autonomous gain or loss, respectively, of blood retina barrier and blood brain barrier function, indicating an ongoing requirement for Frizzled signaling in barrier maintenance and substantial plasticity in mature CNS vascular structure.
Yanshu Wang; Amir Rattner; Yulian Zhou; John Williams; Philip M Smallwood; Jeremy Nathans
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell     Volume:  151     ISSN:  1097-4172     ISO Abbreviation:  Cell     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-10     Completed Date:  2013-02-06     Revised Date:  2014-09-15    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1332-44     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Blood-Brain Barrier*
Blood-Retinal Barrier*
Cell Movement
Cell Proliferation
Endothelial Cells / cytology,  metabolism*
Eye Proteins / genetics,  metabolism*
Frizzled Receptors / genetics,  metabolism*
Nerve Tissue Proteins / genetics,  metabolism*
Neuronal Plasticity
Retina / cytology,  embryology,  metabolism*
Signal Transduction*
Vascular Endothelial Growth Factor A / metabolism
Grant Support
R01 EY018637/EY/NEI NIH HHS; //Howard Hughes Medical Institute
Reg. No./Substance:
0/Eye Proteins; 0/Frizzled Receptors; 0/Fzd4 protein, mouse; 0/Ndph protein, mouse; 0/Nerve Tissue Proteins; 0/VEGFA protein, human; 0/Vascular Endothelial Growth Factor A

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