| Norrin/Frizzled4 signaling in retinal vascular development and blood brain barrier plasticity. | |
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MedLine Citation:
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PMID: 23217714 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Yanshu Wang; Amir Rattner; Yulian Zhou; John Williams; Philip M Smallwood; Jeremy Nathans |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cell Volume: 151 ISSN: 1097-4172 ISO Abbreviation: Cell Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-12-10 Completed Date: 2013-02-06 Revised Date: 2013-06-11 |
Medline Journal Info:
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Nlm Unique ID: 0413066 Medline TA: Cell Country: United States |
Other Details:
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Languages: eng Pagination: 1332-44 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood-Brain Barrier* Blood-Retinal Barrier* Cell Movement Cell Proliferation Endothelial Cells / cytology, metabolism* Eye Proteins / genetics, metabolism* Frizzled Receptors / genetics, metabolism* Humans Mice Mosaicism Nerve Tissue Proteins / genetics, metabolism* Neuronal Plasticity Retina / cytology, embryology, metabolism* Signal Transduction* Vascular Endothelial Growth Factor A / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01 EY018637/EY/NEI NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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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 |
| Comments/Corrections | |
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