title: The contribution of CXCL12-expressing radial glia cells to neuro-vascular patterning during human cerebral cortex development.
abstract: 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.
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari School of Medicine Bari, Italy.
authors.forename: Mariella
authors.initials: M
authors.lastname: Errede
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari School of Medicine Bari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Girolamo
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari School of Medicine Bari, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Rizzi
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari School of Medicine Bari, Italy.
authors.forename: Mirella
authors.initials: M
authors.lastname: Bertossi
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari School of Medicine Bari, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Roncali
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari School of Medicine Bari, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Virgintino
keywords: blood-brain barrier; chemokine CXCL12; connexin 43; human fetus; neuroangiogenesis; radial glia; tight junctions; transporters