Loading…

Fine-Tuning of Sox17 and Canonical Wnt Coordinates the Permeability Properties of the Blood-Brain Barrier

RATIONALE:The microvasculature of the central nervous system includes the blood-brain barrier (BBB), which regulates the permeability to nutrients and restricts the passage of toxic agents and inflammatory cells. Canonical Wnt/β-catenin signaling is responsible for the early phases of brain vascular...

Full description

Saved in:
Bibliographic Details
Published in:Circulation research 2019-02, Vol.124 (4), p.511-525
Main Authors: Corada, Monica, Orsenigo, Fabrizio, Bhat, Ganesh Parameshwar, Conze, Lei Liu, Breviario, Ferruccio, Cunha, Sara Isabel, Claesson-Welsh, Lena, Beznoussenko, Galina V, Mironov, Alexander A, Bacigaluppi, Marco, Martino, Gianvito, Pitulescu, Mara E, Adams, Ralf H, Magnusson, Peetra, Dejana, Elisabetta
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c5597-9526137a27e7b0630eea8937bf196ed1796488ea35e0e3b42edeb50eec315e8a3
cites cdi_FETCH-LOGICAL-c5597-9526137a27e7b0630eea8937bf196ed1796488ea35e0e3b42edeb50eec315e8a3
container_end_page 525
container_issue 4
container_start_page 511
container_title Circulation research
container_volume 124
creator Corada, Monica
Orsenigo, Fabrizio
Bhat, Ganesh Parameshwar
Conze, Lei Liu
Breviario, Ferruccio
Cunha, Sara Isabel
Claesson-Welsh, Lena
Beznoussenko, Galina V
Mironov, Alexander A
Bacigaluppi, Marco
Martino, Gianvito
Pitulescu, Mara E
Adams, Ralf H
Magnusson, Peetra
Dejana, Elisabetta
description RATIONALE:The microvasculature of the central nervous system includes the blood-brain barrier (BBB), which regulates the permeability to nutrients and restricts the passage of toxic agents and inflammatory cells. Canonical Wnt/β-catenin signaling is responsible for the early phases of brain vascularization and BBB differentiation. However, this signal declines after birth, and other signaling pathways able to maintain barrier integrity at postnatal stage are still unknown. OBJECTIVE:Sox17 (SRY [sex-determining region Y]-box 17) constitutes a major downstream target of Wnt/β-catenin in endothelial cells and regulates arterial differentiation. In the present article, we asked whether Sox17 may act downstream of Wnt/β-catenin in inducing BBB differentiation and maintenance. METHODS AND RESULTS:Using reporter mice and nuclear staining of Sox17 and β-catenin, we report that although β-catenin signaling declines after birth, Sox17 activation increases and remains high in the adult. Endothelial-specific inactivation of Sox17 leads to increase of permeability of the brain microcirculation. The severity of this effect depends on the degree of BBB maturationit is strong in the embryo and progressively declines after birth. In search of Sox17 mechanism of action, RNA sequencing analysis of gene expression of brain endothelial cells has identified members of the Wnt/β-catenin signaling pathway as downstream targets of Sox17. Consistently, we found that Sox17 is a positive inducer of Wnt/β-catenin signaling, and it acts in concert with this pathway to induce and maintain BBB properties. In vivo, inhibition of the β-catenin destruction complex or expression of a degradation-resistant β-catenin mutant, prevent the increase in permeability and retina vascular malformations observed in the absence of Sox17. CONCLUSIONS:Our data highlight a novel role for Sox17 in the induction and maintenance of the BBB, and they underline the strict reciprocal tuning of this transcription factor and Wnt/β-catenin pathway. Modulation of Sox17 activity may be relevant to control BBB permeability in pathological conditions.
doi_str_mv 10.1161/CIRCRESAHA.118.313316
format article
fullrecord <record><control><sourceid>pubmed_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_DiVA_org_uu_378993</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>30591003</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5597-9526137a27e7b0630eea8937bf196ed1796488ea35e0e3b42edeb50eec315e8a3</originalsourceid><addsrcrecordid>eNpVkdFu1DAQRS0EokvhE0D-AFJm4jiOX5B205ZWqkTVFni0nGR215C1V07C0r_HVaDQp9HMPffOw2XsLcIJYokf6sub-ubsdnmxTHt1IlAILJ-xBcq8yAqp8DlbAIDOlBBwxF4Nw3cALESuX7IjAVIjgFgwd-48ZXeTd37Dw5rfhl-ouPUdr60P3rW259_8yOsQYue8HWng45b4NcUd2cb1brzn1zHsKY4uaSniQV71IXTZKlrn-crG6Ci-Zi_Wth_ozZ95zL6cn93VF9nV50-X9fIqa6XUKtMyL1EomytSDZQCiGylhWrWqEvqUOmyqCqyQhKQaIqcOmpkolqBkiorjtn7OXc40H5qzD66nY33JlhnTt3XpQlxY6bJCFVpLRL-ccYTu6OuJT9G2z9xPVW825pN-GnKAlQFOgXIOaCNYRgirR-9COahKvOvqrRXZq4q-d79__jR9bebBBQzcAj9SHH40U8HimZLth-3JnULAjDPckANOUrI0gWV-A2uSaFs</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Fine-Tuning of Sox17 and Canonical Wnt Coordinates the Permeability Properties of the Blood-Brain Barrier</title><source>Free E- Journals</source><creator>Corada, Monica ; Orsenigo, Fabrizio ; Bhat, Ganesh Parameshwar ; Conze, Lei Liu ; Breviario, Ferruccio ; Cunha, Sara Isabel ; Claesson-Welsh, Lena ; Beznoussenko, Galina V ; Mironov, Alexander A ; Bacigaluppi, Marco ; Martino, Gianvito ; Pitulescu, Mara E ; Adams, Ralf H ; Magnusson, Peetra ; Dejana, Elisabetta</creator><creatorcontrib>Corada, Monica ; Orsenigo, Fabrizio ; Bhat, Ganesh Parameshwar ; Conze, Lei Liu ; Breviario, Ferruccio ; Cunha, Sara Isabel ; Claesson-Welsh, Lena ; Beznoussenko, Galina V ; Mironov, Alexander A ; Bacigaluppi, Marco ; Martino, Gianvito ; Pitulescu, Mara E ; Adams, Ralf H ; Magnusson, Peetra ; Dejana, Elisabetta</creatorcontrib><description>RATIONALE:The microvasculature of the central nervous system includes the blood-brain barrier (BBB), which regulates the permeability to nutrients and restricts the passage of toxic agents and inflammatory cells. Canonical Wnt/β-catenin signaling is responsible for the early phases of brain vascularization and BBB differentiation. However, this signal declines after birth, and other signaling pathways able to maintain barrier integrity at postnatal stage are still unknown. OBJECTIVE:Sox17 (SRY [sex-determining region Y]-box 17) constitutes a major downstream target of Wnt/β-catenin in endothelial cells and regulates arterial differentiation. In the present article, we asked whether Sox17 may act downstream of Wnt/β-catenin in inducing BBB differentiation and maintenance. METHODS AND RESULTS:Using reporter mice and nuclear staining of Sox17 and β-catenin, we report that although β-catenin signaling declines after birth, Sox17 activation increases and remains high in the adult. Endothelial-specific inactivation of Sox17 leads to increase of permeability of the brain microcirculation. The severity of this effect depends on the degree of BBB maturationit is strong in the embryo and progressively declines after birth. In search of Sox17 mechanism of action, RNA sequencing analysis of gene expression of brain endothelial cells has identified members of the Wnt/β-catenin signaling pathway as downstream targets of Sox17. Consistently, we found that Sox17 is a positive inducer of Wnt/β-catenin signaling, and it acts in concert with this pathway to induce and maintain BBB properties. In vivo, inhibition of the β-catenin destruction complex or expression of a degradation-resistant β-catenin mutant, prevent the increase in permeability and retina vascular malformations observed in the absence of Sox17. CONCLUSIONS:Our data highlight a novel role for Sox17 in the induction and maintenance of the BBB, and they underline the strict reciprocal tuning of this transcription factor and Wnt/β-catenin pathway. Modulation of Sox17 activity may be relevant to control BBB permeability in pathological conditions.</description><identifier>ISSN: 0009-7330</identifier><identifier>ISSN: 1524-4571</identifier><identifier>EISSN: 1524-4571</identifier><identifier>DOI: 10.1161/CIRCRESAHA.118.313316</identifier><identifier>PMID: 30591003</identifier><language>eng</language><publisher>United States: American Heart Association, Inc</publisher><subject>Animals ; blood-brain barrier ; Blood-Brain Barrier - metabolism ; Capillary Permeability ; Cellular Biology ; endothelial cells ; HMGB Proteins - genetics ; HMGB Proteins - metabolism ; Mice ; Mice, Inbred C57BL ; permeability ; SOXF Transcription Factors - genetics ; SOXF Transcription Factors - metabolism ; stroke ; Wnt Signaling Pathway ; Wnt/beta-catenin</subject><ispartof>Circulation research, 2019-02, Vol.124 (4), p.511-525</ispartof><rights>2019 American Heart Association, Inc.</rights><rights>2018 The Authors. 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5597-9526137a27e7b0630eea8937bf196ed1796488ea35e0e3b42edeb50eec315e8a3</citedby><cites>FETCH-LOGICAL-c5597-9526137a27e7b0630eea8937bf196ed1796488ea35e0e3b42edeb50eec315e8a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30591003$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-378993$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Corada, Monica</creatorcontrib><creatorcontrib>Orsenigo, Fabrizio</creatorcontrib><creatorcontrib>Bhat, Ganesh Parameshwar</creatorcontrib><creatorcontrib>Conze, Lei Liu</creatorcontrib><creatorcontrib>Breviario, Ferruccio</creatorcontrib><creatorcontrib>Cunha, Sara Isabel</creatorcontrib><creatorcontrib>Claesson-Welsh, Lena</creatorcontrib><creatorcontrib>Beznoussenko, Galina V</creatorcontrib><creatorcontrib>Mironov, Alexander A</creatorcontrib><creatorcontrib>Bacigaluppi, Marco</creatorcontrib><creatorcontrib>Martino, Gianvito</creatorcontrib><creatorcontrib>Pitulescu, Mara E</creatorcontrib><creatorcontrib>Adams, Ralf H</creatorcontrib><creatorcontrib>Magnusson, Peetra</creatorcontrib><creatorcontrib>Dejana, Elisabetta</creatorcontrib><title>Fine-Tuning of Sox17 and Canonical Wnt Coordinates the Permeability Properties of the Blood-Brain Barrier</title><title>Circulation research</title><addtitle>Circ Res</addtitle><description>RATIONALE:The microvasculature of the central nervous system includes the blood-brain barrier (BBB), which regulates the permeability to nutrients and restricts the passage of toxic agents and inflammatory cells. Canonical Wnt/β-catenin signaling is responsible for the early phases of brain vascularization and BBB differentiation. However, this signal declines after birth, and other signaling pathways able to maintain barrier integrity at postnatal stage are still unknown. OBJECTIVE:Sox17 (SRY [sex-determining region Y]-box 17) constitutes a major downstream target of Wnt/β-catenin in endothelial cells and regulates arterial differentiation. In the present article, we asked whether Sox17 may act downstream of Wnt/β-catenin in inducing BBB differentiation and maintenance. METHODS AND RESULTS:Using reporter mice and nuclear staining of Sox17 and β-catenin, we report that although β-catenin signaling declines after birth, Sox17 activation increases and remains high in the adult. Endothelial-specific inactivation of Sox17 leads to increase of permeability of the brain microcirculation. The severity of this effect depends on the degree of BBB maturationit is strong in the embryo and progressively declines after birth. In search of Sox17 mechanism of action, RNA sequencing analysis of gene expression of brain endothelial cells has identified members of the Wnt/β-catenin signaling pathway as downstream targets of Sox17. Consistently, we found that Sox17 is a positive inducer of Wnt/β-catenin signaling, and it acts in concert with this pathway to induce and maintain BBB properties. In vivo, inhibition of the β-catenin destruction complex or expression of a degradation-resistant β-catenin mutant, prevent the increase in permeability and retina vascular malformations observed in the absence of Sox17. CONCLUSIONS:Our data highlight a novel role for Sox17 in the induction and maintenance of the BBB, and they underline the strict reciprocal tuning of this transcription factor and Wnt/β-catenin pathway. Modulation of Sox17 activity may be relevant to control BBB permeability in pathological conditions.</description><subject>Animals</subject><subject>blood-brain barrier</subject><subject>Blood-Brain Barrier - metabolism</subject><subject>Capillary Permeability</subject><subject>Cellular Biology</subject><subject>endothelial cells</subject><subject>HMGB Proteins - genetics</subject><subject>HMGB Proteins - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>permeability</subject><subject>SOXF Transcription Factors - genetics</subject><subject>SOXF Transcription Factors - metabolism</subject><subject>stroke</subject><subject>Wnt Signaling Pathway</subject><subject>Wnt/beta-catenin</subject><issn>0009-7330</issn><issn>1524-4571</issn><issn>1524-4571</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNpVkdFu1DAQRS0EokvhE0D-AFJm4jiOX5B205ZWqkTVFni0nGR215C1V07C0r_HVaDQp9HMPffOw2XsLcIJYokf6sub-ubsdnmxTHt1IlAILJ-xBcq8yAqp8DlbAIDOlBBwxF4Nw3cALESuX7IjAVIjgFgwd-48ZXeTd37Dw5rfhl-ouPUdr60P3rW259_8yOsQYue8HWng45b4NcUd2cb1brzn1zHsKY4uaSniQV71IXTZKlrn-crG6Ci-Zi_Wth_ozZ95zL6cn93VF9nV50-X9fIqa6XUKtMyL1EomytSDZQCiGylhWrWqEvqUOmyqCqyQhKQaIqcOmpkolqBkiorjtn7OXc40H5qzD66nY33JlhnTt3XpQlxY6bJCFVpLRL-ccYTu6OuJT9G2z9xPVW825pN-GnKAlQFOgXIOaCNYRgirR-9COahKvOvqrRXZq4q-d79__jR9bebBBQzcAj9SHH40U8HimZLth-3JnULAjDPckANOUrI0gWV-A2uSaFs</recordid><startdate>20190215</startdate><enddate>20190215</enddate><creator>Corada, Monica</creator><creator>Orsenigo, Fabrizio</creator><creator>Bhat, Ganesh Parameshwar</creator><creator>Conze, Lei Liu</creator><creator>Breviario, Ferruccio</creator><creator>Cunha, Sara Isabel</creator><creator>Claesson-Welsh, Lena</creator><creator>Beznoussenko, Galina V</creator><creator>Mironov, Alexander A</creator><creator>Bacigaluppi, Marco</creator><creator>Martino, Gianvito</creator><creator>Pitulescu, Mara E</creator><creator>Adams, Ralf H</creator><creator>Magnusson, Peetra</creator><creator>Dejana, Elisabetta</creator><general>American Heart Association, Inc</general><general>Lippincott Williams &amp; Wilkins</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope><scope>ACNBI</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>DF2</scope><scope>ZZAVC</scope></search><sort><creationdate>20190215</creationdate><title>Fine-Tuning of Sox17 and Canonical Wnt Coordinates the Permeability Properties of the Blood-Brain Barrier</title><author>Corada, Monica ; Orsenigo, Fabrizio ; Bhat, Ganesh Parameshwar ; Conze, Lei Liu ; Breviario, Ferruccio ; Cunha, Sara Isabel ; Claesson-Welsh, Lena ; Beznoussenko, Galina V ; Mironov, Alexander A ; Bacigaluppi, Marco ; Martino, Gianvito ; Pitulescu, Mara E ; Adams, Ralf H ; Magnusson, Peetra ; Dejana, Elisabetta</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5597-9526137a27e7b0630eea8937bf196ed1796488ea35e0e3b42edeb50eec315e8a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>blood-brain barrier</topic><topic>Blood-Brain Barrier - metabolism</topic><topic>Capillary Permeability</topic><topic>Cellular Biology</topic><topic>endothelial cells</topic><topic>HMGB Proteins - genetics</topic><topic>HMGB Proteins - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>permeability</topic><topic>SOXF Transcription Factors - genetics</topic><topic>SOXF Transcription Factors - metabolism</topic><topic>stroke</topic><topic>Wnt Signaling Pathway</topic><topic>Wnt/beta-catenin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Corada, Monica</creatorcontrib><creatorcontrib>Orsenigo, Fabrizio</creatorcontrib><creatorcontrib>Bhat, Ganesh Parameshwar</creatorcontrib><creatorcontrib>Conze, Lei Liu</creatorcontrib><creatorcontrib>Breviario, Ferruccio</creatorcontrib><creatorcontrib>Cunha, Sara Isabel</creatorcontrib><creatorcontrib>Claesson-Welsh, Lena</creatorcontrib><creatorcontrib>Beznoussenko, Galina V</creatorcontrib><creatorcontrib>Mironov, Alexander A</creatorcontrib><creatorcontrib>Bacigaluppi, Marco</creatorcontrib><creatorcontrib>Martino, Gianvito</creatorcontrib><creatorcontrib>Pitulescu, Mara E</creatorcontrib><creatorcontrib>Adams, Ralf H</creatorcontrib><creatorcontrib>Magnusson, Peetra</creatorcontrib><creatorcontrib>Dejana, Elisabetta</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SWEPUB Uppsala universitet full text</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SWEPUB Uppsala universitet</collection><collection>SwePub Articles full text</collection><jtitle>Circulation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Corada, Monica</au><au>Orsenigo, Fabrizio</au><au>Bhat, Ganesh Parameshwar</au><au>Conze, Lei Liu</au><au>Breviario, Ferruccio</au><au>Cunha, Sara Isabel</au><au>Claesson-Welsh, Lena</au><au>Beznoussenko, Galina V</au><au>Mironov, Alexander A</au><au>Bacigaluppi, Marco</au><au>Martino, Gianvito</au><au>Pitulescu, Mara E</au><au>Adams, Ralf H</au><au>Magnusson, Peetra</au><au>Dejana, Elisabetta</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fine-Tuning of Sox17 and Canonical Wnt Coordinates the Permeability Properties of the Blood-Brain Barrier</atitle><jtitle>Circulation research</jtitle><addtitle>Circ Res</addtitle><date>2019-02-15</date><risdate>2019</risdate><volume>124</volume><issue>4</issue><spage>511</spage><epage>525</epage><pages>511-525</pages><issn>0009-7330</issn><issn>1524-4571</issn><eissn>1524-4571</eissn><abstract>RATIONALE:The microvasculature of the central nervous system includes the blood-brain barrier (BBB), which regulates the permeability to nutrients and restricts the passage of toxic agents and inflammatory cells. Canonical Wnt/β-catenin signaling is responsible for the early phases of brain vascularization and BBB differentiation. However, this signal declines after birth, and other signaling pathways able to maintain barrier integrity at postnatal stage are still unknown. OBJECTIVE:Sox17 (SRY [sex-determining region Y]-box 17) constitutes a major downstream target of Wnt/β-catenin in endothelial cells and regulates arterial differentiation. In the present article, we asked whether Sox17 may act downstream of Wnt/β-catenin in inducing BBB differentiation and maintenance. METHODS AND RESULTS:Using reporter mice and nuclear staining of Sox17 and β-catenin, we report that although β-catenin signaling declines after birth, Sox17 activation increases and remains high in the adult. Endothelial-specific inactivation of Sox17 leads to increase of permeability of the brain microcirculation. The severity of this effect depends on the degree of BBB maturationit is strong in the embryo and progressively declines after birth. In search of Sox17 mechanism of action, RNA sequencing analysis of gene expression of brain endothelial cells has identified members of the Wnt/β-catenin signaling pathway as downstream targets of Sox17. Consistently, we found that Sox17 is a positive inducer of Wnt/β-catenin signaling, and it acts in concert with this pathway to induce and maintain BBB properties. In vivo, inhibition of the β-catenin destruction complex or expression of a degradation-resistant β-catenin mutant, prevent the increase in permeability and retina vascular malformations observed in the absence of Sox17. CONCLUSIONS:Our data highlight a novel role for Sox17 in the induction and maintenance of the BBB, and they underline the strict reciprocal tuning of this transcription factor and Wnt/β-catenin pathway. Modulation of Sox17 activity may be relevant to control BBB permeability in pathological conditions.</abstract><cop>United States</cop><pub>American Heart Association, Inc</pub><pmid>30591003</pmid><doi>10.1161/CIRCRESAHA.118.313316</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0009-7330
ispartof Circulation research, 2019-02, Vol.124 (4), p.511-525
issn 0009-7330
1524-4571
1524-4571
language eng
recordid cdi_swepub_primary_oai_DiVA_org_uu_378993
source Free E- Journals
subjects Animals
blood-brain barrier
Blood-Brain Barrier - metabolism
Capillary Permeability
Cellular Biology
endothelial cells
HMGB Proteins - genetics
HMGB Proteins - metabolism
Mice
Mice, Inbred C57BL
permeability
SOXF Transcription Factors - genetics
SOXF Transcription Factors - metabolism
stroke
Wnt Signaling Pathway
Wnt/beta-catenin
title Fine-Tuning of Sox17 and Canonical Wnt Coordinates the Permeability Properties of the Blood-Brain Barrier
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T12%3A17%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_swepu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Fine-Tuning%20of%20Sox17%20and%20Canonical%20Wnt%20Coordinates%20the%20Permeability%20Properties%20of%20the%20Blood-Brain%20Barrier&rft.jtitle=Circulation%20research&rft.au=Corada,%20Monica&rft.date=2019-02-15&rft.volume=124&rft.issue=4&rft.spage=511&rft.epage=525&rft.pages=511-525&rft.issn=0009-7330&rft.eissn=1524-4571&rft_id=info:doi/10.1161/CIRCRESAHA.118.313316&rft_dat=%3Cpubmed_swepu%3E30591003%3C/pubmed_swepu%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c5597-9526137a27e7b0630eea8937bf196ed1796488ea35e0e3b42edeb50eec315e8a3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_id=info:pmid/30591003&rfr_iscdi=true