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Interplay of the Norrin and Wnt7a/Wnt7b signaling systems in blood–brain barrier and blood–retina barrier development and maintenance
by
Wang, Yanshu
, Nathans, Jeremy
, Zhang, Chi
, Junge, Harald J.
, Smallwood, Philip M.
, Cho, Chris
, Williams, John
in
Animals
/ Barriers
/ beta Catenin - physiology
/ Biological Sciences
/ Blood
/ Blood-brain barrier
/ Blood-Brain Barrier - cytology
/ Blood-Brain Barrier - growth & development
/ Blood-Brain Barrier - physiology
/ Blood-Retinal Barrier - cytology
/ Blood-Retinal Barrier - growth & development
/ Blood-Retinal Barrier - physiology
/ Brain
/ Cell Culture Techniques
/ Cerebellum
/ Division of labor
/ Endothelial cells
/ Eye Proteins - genetics
/ Eye Proteins - physiology
/ Frizzled Receptors - deficiency
/ Frizzled Receptors - genetics
/ Frizzled Receptors - physiology
/ Genetic analysis
/ Heterogeneity
/ Ligands
/ Maintenance
/ Mice
/ Mice, Knockout
/ Models, Biological
/ Models, Neurological
/ Nerve Tissue Proteins - deficiency
/ Nerve Tissue Proteins - genetics
/ Nerve Tissue Proteins - physiology
/ Nervous system
/ Neuroscience
/ Phenotypes
/ PNAS Plus
/ Proto-Oncogene Proteins - deficiency
/ Proto-Oncogene Proteins - genetics
/ Proto-Oncogene Proteins - physiology
/ Receptors
/ Redundancy
/ Retina
/ Rodents
/ Signal Transduction
/ Signalling systems
/ Tetraspanins - deficiency
/ Tetraspanins - genetics
/ Tetraspanins - physiology
/ Vascular endothelial growth factor
/ Wnt Proteins - deficiency
/ Wnt Proteins - genetics
/ Wnt Proteins - physiology
/ β-Catenin
2018
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Interplay of the Norrin and Wnt7a/Wnt7b signaling systems in blood–brain barrier and blood–retina barrier development and maintenance
by
Wang, Yanshu
, Nathans, Jeremy
, Zhang, Chi
, Junge, Harald J.
, Smallwood, Philip M.
, Cho, Chris
, Williams, John
in
Animals
/ Barriers
/ beta Catenin - physiology
/ Biological Sciences
/ Blood
/ Blood-brain barrier
/ Blood-Brain Barrier - cytology
/ Blood-Brain Barrier - growth & development
/ Blood-Brain Barrier - physiology
/ Blood-Retinal Barrier - cytology
/ Blood-Retinal Barrier - growth & development
/ Blood-Retinal Barrier - physiology
/ Brain
/ Cell Culture Techniques
/ Cerebellum
/ Division of labor
/ Endothelial cells
/ Eye Proteins - genetics
/ Eye Proteins - physiology
/ Frizzled Receptors - deficiency
/ Frizzled Receptors - genetics
/ Frizzled Receptors - physiology
/ Genetic analysis
/ Heterogeneity
/ Ligands
/ Maintenance
/ Mice
/ Mice, Knockout
/ Models, Biological
/ Models, Neurological
/ Nerve Tissue Proteins - deficiency
/ Nerve Tissue Proteins - genetics
/ Nerve Tissue Proteins - physiology
/ Nervous system
/ Neuroscience
/ Phenotypes
/ PNAS Plus
/ Proto-Oncogene Proteins - deficiency
/ Proto-Oncogene Proteins - genetics
/ Proto-Oncogene Proteins - physiology
/ Receptors
/ Redundancy
/ Retina
/ Rodents
/ Signal Transduction
/ Signalling systems
/ Tetraspanins - deficiency
/ Tetraspanins - genetics
/ Tetraspanins - physiology
/ Vascular endothelial growth factor
/ Wnt Proteins - deficiency
/ Wnt Proteins - genetics
/ Wnt Proteins - physiology
/ β-Catenin
2018
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Interplay of the Norrin and Wnt7a/Wnt7b signaling systems in blood–brain barrier and blood–retina barrier development and maintenance
by
Wang, Yanshu
, Nathans, Jeremy
, Zhang, Chi
, Junge, Harald J.
, Smallwood, Philip M.
, Cho, Chris
, Williams, John
in
Animals
/ Barriers
/ beta Catenin - physiology
/ Biological Sciences
/ Blood
/ Blood-brain barrier
/ Blood-Brain Barrier - cytology
/ Blood-Brain Barrier - growth & development
/ Blood-Brain Barrier - physiology
/ Blood-Retinal Barrier - cytology
/ Blood-Retinal Barrier - growth & development
/ Blood-Retinal Barrier - physiology
/ Brain
/ Cell Culture Techniques
/ Cerebellum
/ Division of labor
/ Endothelial cells
/ Eye Proteins - genetics
/ Eye Proteins - physiology
/ Frizzled Receptors - deficiency
/ Frizzled Receptors - genetics
/ Frizzled Receptors - physiology
/ Genetic analysis
/ Heterogeneity
/ Ligands
/ Maintenance
/ Mice
/ Mice, Knockout
/ Models, Biological
/ Models, Neurological
/ Nerve Tissue Proteins - deficiency
/ Nerve Tissue Proteins - genetics
/ Nerve Tissue Proteins - physiology
/ Nervous system
/ Neuroscience
/ Phenotypes
/ PNAS Plus
/ Proto-Oncogene Proteins - deficiency
/ Proto-Oncogene Proteins - genetics
/ Proto-Oncogene Proteins - physiology
/ Receptors
/ Redundancy
/ Retina
/ Rodents
/ Signal Transduction
/ Signalling systems
/ Tetraspanins - deficiency
/ Tetraspanins - genetics
/ Tetraspanins - physiology
/ Vascular endothelial growth factor
/ Wnt Proteins - deficiency
/ Wnt Proteins - genetics
/ Wnt Proteins - physiology
/ β-Catenin
2018
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Interplay of the Norrin and Wnt7a/Wnt7b signaling systems in blood–brain barrier and blood–retina barrier development and maintenance
Journal Article
Interplay of the Norrin and Wnt7a/Wnt7b signaling systems in blood–brain barrier and blood–retina barrier development and maintenance
2018
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Overview
β-Catenin signaling controls the development and maintenance of the blood–brain barrier (BBB) and the blood–retina barrier (BRB), but the division of labor and degree of redundancy between the two principal ligand–receptor systems—the Norrin and Wnt7a/Wnt7b systems—are incompletely defined. Here, we present a loss-of-function genetic analysis of postnatal BBB and BRB maintenance in mice that shows striking threshold and partial redundancy effects. In particular, the combined loss of Wnt7a and Norrin or Wnt7a and Frizzled4 (Fz4) leads to anatomically localized BBB defects that are far more severe than observed with loss of Wnt7a, Norrin, or Fz4 alone. In the cerebellum, selective loss of Wnt7a in glia combined with ubiquitous loss of Norrin recapitulates the phenotype observed with ubiquitous loss of both Wnt7a and Norrin, implying that glia are the source of Wnt7a in the cerebellum. Tspan12, a coactivator of Norrin signaling in the retina, is also active in BBB maintenance but is less potent than Norrin, consistent with a model in which Tspan12 enhances the amplitude of the Norrin signal in vascular endothelial cells. Finally, in the context of a partially impaired Norrin system, the retina reveals a small contribution to BRB development from the Wnt7a/Wnt7b system. Taken together, these experiments define the extent of CNS region-specific cooperation for several components of the Norrin and Wnt7a/Wnt7b systems, and they reveal substantial regional heterogeneity in the extent to which partially redundant ligands, receptors, and coactivators maintain the BBB and BRB.
Publisher
National Academy of Sciences
Subject
/ Barriers
/ Blood
/ Blood-Brain Barrier - cytology
/ Blood-Brain Barrier - growth & development
/ Blood-Brain Barrier - physiology
/ Blood-Retinal Barrier - cytology
/ Blood-Retinal Barrier - growth & development
/ Blood-Retinal Barrier - physiology
/ Brain
/ Frizzled Receptors - deficiency
/ Frizzled Receptors - genetics
/ Frizzled Receptors - physiology
/ Ligands
/ Mice
/ Nerve Tissue Proteins - deficiency
/ Nerve Tissue Proteins - genetics
/ Nerve Tissue Proteins - physiology
/ Proto-Oncogene Proteins - deficiency
/ Proto-Oncogene Proteins - genetics
/ Proto-Oncogene Proteins - physiology
/ Retina
/ Rodents
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