title: CXCR4 signaling regulates radial glial morphology and cell fate during embryonic spinal cord development.
abstract: Embryonic meninges secrete the chemokine SDF-1/CXCL12 as a chemotactic guide for migrating neural stem cells, but SDF-1 is not known to directly regulate the functions of radial glia. Recently, the developing meninges have been shown to regulate radial glial function, yet the mechanisms and signals responsible for this phenomenon remain unclear. Moreover, as a nonmigratory cell type, radial glia do not conform to traditional models associated with chemokine signaling in the central nervous system. Using fluorescent transgenes, in vivo genetic manipulations and pharmacological techniques, we demonstrate that SDF-1 derived from the meninges exerts a CXCR4-dependent effect on radial glia. Deletion of CXCR4 expression by radial glia influences their morphology, mitosis, and progression through both oligodendroglial and astroglial lineages. Additionally, disruption of CXCR4 signaling in radial glia has a transient effect on the migration of oligodendrocyte progenitors. These data indicate that a specific chemokine signal derived from the meninges has multiple regulatory effects on radial glia.
authors.affiliation: Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, 303 E Chicago Ave, Chicago, IL 60611, USA.
authors.forename: Divakar S
authors.initials: DS
authors.lastname: Mithal
authors.forename: Dongjun
authors.initials: D
authors.lastname: Ren
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Miller
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000502:physiology; D002465:Cell Movement / Q000235:genetics; D063928:Ependymoglial Cells / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D005260:Female; D018345:Mice, Knockout; D008938:Mitosis / Q000235:genetics; D058953:Neural Stem Cells / Q000502:physiology*; D009924:Organ Culture Techniques; D011247:Pregnancy; D019718:Receptors, CXCR4 / Q000172:deficiency* / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology* / Q000502:physiology*; D019076:Transgenes
chemical_list: D019718:Receptors, CXCR4
keywords: CXCR4; SDF-1; chemokine receptor; oligodendrocyte progenitor; radial glia