title: Chemokine Signaling Controls Integrity of Radial Glial Scaffold in Developing Spinal Cord and Consequential Proper Position of Boundary Cap Cells.
abstract: Radial glial cells are the neural progenitors of the developing CNS and have long radial processes that guide radially migrating neurons. The integrity of the radial glial scaffold, in particular proper adhesion between the endfeet of radial processes and the pial basement membrane (BM), is important for the cellular organization of the CNS, as indicated by evidence emerging from the developing cortex. However, the mechanisms underlying the maintenance of radial glial scaffold integrity during development, when the neuroepithelium rapidly expands, are still poorly understood. Here, we addressed this issue in the developing mouse spinal cord. We show that CXCR4, a receptor of chemokine CXCL12, is expressed in spinal cord radial glia. Conditional knock-out of Cxcr4 in radial glia caused disrupted radial glial scaffold with gaps at the pial endfeet layer and consequentially led to an invasion of boundary cap (BC) cells into the spinal cord. Because BC cells are PNS cells normally positioned at the incoming and outgoing axonal roots, their invasion into the spinal cord suggests a compromised CNS/PNS boundary in the absence of CXCL12/CXCR4 signaling. Both disrupted radial glial scaffold and invasion of BC cells into the CNS were also present in mice deficient in CXCR7, a second receptor of CXCL12. We further show that CXCL12 signaling promotes the radial glia adhesion to BM components and activates integrin β1 avidity. Our study unravels a novel molecular mechanism that deploys CXCL12/CXCR4/CXCR7 for the maintenance of radial glial scaffold integrity, which in turn safeguards the CNS/PNS boundary during spinal cord development.
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan, yan-zhu@umin.ac.jp.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Immunobiology and Hematology, Institute for Frontier Medical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan, and.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagasawa
authors.affiliation: Department of Immunology, Monash University, Central Clinical School, Alfred Medical Research and Education Precinct, Melbourne, Victoria 3004, Australia.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Mackay
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Fujio
authors.initials: F
authors.lastname: Murakami
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D063928:Ependymoglial Cells / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009457:Neuroglia / Q000378:metabolism; D038081:Organogenesis / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000172:deficiency*; D015398:Signal Transduction / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*
chemical_list: C514936:CXCR4 protein, mouse; D019718:Receptors, CXCR4
keywords: CXCL12; CXCR4; boundary cap cells; integrin b1; pial endfeet; radial glia