TY - JOUR
T1 - Beta-catenin signaling regulates barrier- specific gene expression in circumventricular organ and ocular vasculatures
AU - Wang, Yanshu
AU - Sabbagh, Mark F.
AU - Gu, Xiaowu
AU - Rattner, Amir
AU - Williams, John
AU - Nathans, Jeremy
N1 - Funding Information:
The authors would like to thank Dr. Maketo Taketo (Kyoto University) for the Ctnnb1flex3 mice, AlexGrinberg (NICHD, NIH) for the Wif1-mice, Robb Krumlauf (Stowers Institute) for Sostdc1-mice, David Silver (Duke-NUS Medical School) for rabbit anti-MFSD2A antiserum, Haiping Hao and Linda Orzolek (Johns Hopkins University Deep Sequencing and Microarray Core Facility) for RNA library preparation and for NextGen sequencing, Michael Delannoy (Johns Hopkins Microscope Core Facility) for assistance with TEM; and Tao-Hsin Chang, Chris Cho, and Jacob Heng for helpful discussions and/or comments on the manuscript. This work was supported by the Howard Hughes Medical Institute, the National Eye Institute (R01 EY018637), and the Arnold and Mabel Beckman Foundation. Howard Hughes Medical Institute National Eye Institute R01 EY018637 Eunice Kennedy Shriver National Institute of Child Health and Human Development Arnold and Mabel Beckman Foundation
Funding Information:
The authors would like to thank Dr. Maketo Taketo (Kyoto University) for the Ctnnb1flex3 mice, Alex Grinberg (NICHD, NIH) for the Wif1-mice, Robb Krumlauf (Stowers Institute) for Sostdc1-mice, David Silver (Duke-NUS Medical School) for rabbit anti-MFSD2A antiserum, Haiping Hao and Linda Orzolek (Johns Hopkins University Deep Sequencing and Microarray Core Facility) for RNA library preparation and for NextGen sequencing, Michael Delannoy (Johns Hopkins Microscope Core Facility) for assistance with TEM; and Tao-Hsin Chang, Chris Cho, and Jacob Heng for helpful discussions and/or comments on the manuscript. This work was supported by the Howard Hughes Medical Institute, the National Eye Institute (R01 EY018637), and the Arnold and Mabel Beckman Foundation.
Publisher Copyright:
© Iordanov et al.
PY - 2019/4
Y1 - 2019/4
N2 - The brain, spinal cord, and retina are supplied by capillaries that do not permit free diffusion of molecules between serum and parenchyma, a property that defines the blood-brain and blood-retina barriers. Exceptions to this pattern are found in circumventricular organs (CVOs), small midline brain structures that are supplied by high permeability capillaries. In the eye and brain, high permeability capillaries are also present in the choriocapillaris, which supplies the retinal pigment epithelium and photoreceptors, and the ciliary body and choroid plexus, the sources of aqueous humor and cerebrospinal fluid, respectively. We show here that (1) endothelial cells in these high permeability vascular systems have very low beta-catenin signaling compared to barrier- competent endothelial cells, and (2) elevating beta-catenin signaling leads to a partial conversion of permeable endothelial cells to a barrier-type state. In one CVO, the area postrema, high permeability is maintained, in part, by local production of Wnt inhibitory factor-1.
AB - The brain, spinal cord, and retina are supplied by capillaries that do not permit free diffusion of molecules between serum and parenchyma, a property that defines the blood-brain and blood-retina barriers. Exceptions to this pattern are found in circumventricular organs (CVOs), small midline brain structures that are supplied by high permeability capillaries. In the eye and brain, high permeability capillaries are also present in the choriocapillaris, which supplies the retinal pigment epithelium and photoreceptors, and the ciliary body and choroid plexus, the sources of aqueous humor and cerebrospinal fluid, respectively. We show here that (1) endothelial cells in these high permeability vascular systems have very low beta-catenin signaling compared to barrier- competent endothelial cells, and (2) elevating beta-catenin signaling leads to a partial conversion of permeable endothelial cells to a barrier-type state. In one CVO, the area postrema, high permeability is maintained, in part, by local production of Wnt inhibitory factor-1.
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U2 - 10.7554/eLife.43257
DO - 10.7554/eLife.43257
M3 - Article
C2 - 30932813
AN - SCOPUS:85064001802
SN - 2050-084X
VL - 8
JO - eLife
JF - eLife
M1 - e43257
ER -