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The contribution of CXCL12-expressing radial glia cells to neuro-vascular patterning during human cerebral cortex development

This study was conducted on human developing brain by laser confocal and transmission electron microscopy (TEM) to make a detailed analysis of important features of blood-brain barrier (BBB) microvessels and possible control mechanisms of vessel growth and differentiation during cerebral cortex vasc...

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Autores principales: Errede, Mariella, Girolamo, Francesco, Rizzi, Marco, Bertossi, Mirella, Roncali, Luisa, Virgintino, Daniela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197642/
https://www.ncbi.nlm.nih.gov/pubmed/25360079
http://dx.doi.org/10.3389/fnins.2014.00324
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author Errede, Mariella
Girolamo, Francesco
Rizzi, Marco
Bertossi, Mirella
Roncali, Luisa
Virgintino, Daniela
author_facet Errede, Mariella
Girolamo, Francesco
Rizzi, Marco
Bertossi, Mirella
Roncali, Luisa
Virgintino, Daniela
author_sort Errede, Mariella
collection PubMed
description This study was conducted on human developing brain by laser confocal and transmission electron microscopy (TEM) to make a detailed analysis of important features of blood-brain barrier (BBB) microvessels and possible control mechanisms of vessel growth and differentiation during cerebral cortex vascularization. The BBB status of cortex microvessels was examined at a defined stage of cortex development, at the end of neuroblast waves of migration, and before cortex lamination, with BBB-endothelial cell markers, namely tight junction (TJ) proteins (occludin and claudin-5) and influx and efflux transporters (Glut-1 and P-glycoprotein), the latter supporting evidence for functional effectiveness of the fetal BBB. According to the well-known roles of astroglia cells on microvessel growth and differentiation, the early composition of astroglia/endothelial cell relationships was analyzed by detecting the appropriate astroglia, endothelial, and pericyte markers. GFAP, chemokine CXCL12, and connexin 43 (Cx43) were utilized as markers of radial glia cells, CD105 (endoglin) as a marker of angiogenically activated endothelial cells (ECs), and proteoglycan NG2 as a marker of immature pericytes. Immunolabeling for CXCL12 showed the highest level of the ligand in radial glial (RG) fibers in contact with the growing cortex microvessels. These specialized contacts, recognizable on both perforating radial vessels and growing collaterals, appeared as CXCL12-reactive en passant, symmetrical and asymmetrical, vessel-specific RG fiber swellings. At the highest confocal resolution, these RG varicosities showed a CXCL12-reactive dot-like content whose microvesicular nature was confirmed by ultrastructural observations. A further analysis of RG varicosities reveals colocalization of CXCL12 with Cx43, which is possibly implicated in vessel-specific chemokine signaling.
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spelling pubmed-41976422014-10-30 The contribution of CXCL12-expressing radial glia cells to neuro-vascular patterning during human cerebral cortex development Errede, Mariella Girolamo, Francesco Rizzi, Marco Bertossi, Mirella Roncali, Luisa Virgintino, Daniela Front Neurosci Genetics This study was conducted on human developing brain by laser confocal and transmission electron microscopy (TEM) to make a detailed analysis of important features of blood-brain barrier (BBB) microvessels and possible control mechanisms of vessel growth and differentiation during cerebral cortex vascularization. The BBB status of cortex microvessels was examined at a defined stage of cortex development, at the end of neuroblast waves of migration, and before cortex lamination, with BBB-endothelial cell markers, namely tight junction (TJ) proteins (occludin and claudin-5) and influx and efflux transporters (Glut-1 and P-glycoprotein), the latter supporting evidence for functional effectiveness of the fetal BBB. According to the well-known roles of astroglia cells on microvessel growth and differentiation, the early composition of astroglia/endothelial cell relationships was analyzed by detecting the appropriate astroglia, endothelial, and pericyte markers. GFAP, chemokine CXCL12, and connexin 43 (Cx43) were utilized as markers of radial glia cells, CD105 (endoglin) as a marker of angiogenically activated endothelial cells (ECs), and proteoglycan NG2 as a marker of immature pericytes. Immunolabeling for CXCL12 showed the highest level of the ligand in radial glial (RG) fibers in contact with the growing cortex microvessels. These specialized contacts, recognizable on both perforating radial vessels and growing collaterals, appeared as CXCL12-reactive en passant, symmetrical and asymmetrical, vessel-specific RG fiber swellings. At the highest confocal resolution, these RG varicosities showed a CXCL12-reactive dot-like content whose microvesicular nature was confirmed by ultrastructural observations. A further analysis of RG varicosities reveals colocalization of CXCL12 with Cx43, which is possibly implicated in vessel-specific chemokine signaling. Frontiers Media S.A. 2014-10-15 /pmc/articles/PMC4197642/ /pubmed/25360079 http://dx.doi.org/10.3389/fnins.2014.00324 Text en Copyright © 2014 Errede, Girolamo, Rizzi, Bertossi, Roncali and Virgintino. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Errede, Mariella
Girolamo, Francesco
Rizzi, Marco
Bertossi, Mirella
Roncali, Luisa
Virgintino, Daniela
The contribution of CXCL12-expressing radial glia cells to neuro-vascular patterning during human cerebral cortex development
title The contribution of CXCL12-expressing radial glia cells to neuro-vascular patterning during human cerebral cortex development
title_full The contribution of CXCL12-expressing radial glia cells to neuro-vascular patterning during human cerebral cortex development
title_fullStr The contribution of CXCL12-expressing radial glia cells to neuro-vascular patterning during human cerebral cortex development
title_full_unstemmed The contribution of CXCL12-expressing radial glia cells to neuro-vascular patterning during human cerebral cortex development
title_short The contribution of CXCL12-expressing radial glia cells to neuro-vascular patterning during human cerebral cortex development
title_sort contribution of cxcl12-expressing radial glia cells to neuro-vascular patterning during human cerebral cortex development
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197642/
https://www.ncbi.nlm.nih.gov/pubmed/25360079
http://dx.doi.org/10.3389/fnins.2014.00324
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