TY - JOUR
T1 - Norrin/Frizzled4 signaling in retinal vascular development and blood brain barrier plasticity
AU - Wang, Yanshu
AU - Rattner, Amir
AU - Zhou, Yulian
AU - Williams, John
AU - Smallwood, Philip M.
AU - Nathans, Jeremy
N1 - Funding Information:
We thank Hugh Cahill, Hao Chang, Alex Kolodkin, Se-Jin Lee, Max Tischfield, and Xin Ye for advice and/or helpful comments on the manuscript. This work was supported by the National Eye Institute (NIH), HHMI, the Johns Hopkins Brain Sciences Institute, the Foundation Fighting Blindness, and the Ellison Medical Foundation.
PY - 2012/12/7
Y1 - 2012/12/7
N2 - 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. PaperClip:
AB - 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. PaperClip:
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U2 - 10.1016/j.cell.2012.10.042
DO - 10.1016/j.cell.2012.10.042
M3 - Article
C2 - 23217714
AN - SCOPUS:84870897220
SN - 0092-8674
VL - 151
SP - 1332
EP - 1344
JO - Cell
JF - Cell
IS - 6
ER -