title: TNFa/TNFR2 signaling is required for glial ensheathment at the dorsal root entry zone.
abstract: Somatosensory information from the periphery is routed to the spinal cord through centrally-projecting sensory axons that cross into the central nervous system (CNS) via the dorsal root entry zone (DREZ). The glial cells that ensheath these axons ensure rapid propagation of this information. Despite the importance of this glial-axon arrangement, how this afferent nerve is assembled during development is unknown. Using in vivo, time-lapse imaging we show that as centrally-projecting pioneer axons from dorsal root ganglia (DRG) enter the spinal cord, they initiate expression of the cytokine TNFalpha. This induction coincides with ensheathment of these axons by associated glia via a TNF receptor 2 (TNFR2)-mediated process. This work identifies a signaling cascade that mediates peripheral glial-axon interactions and it functions to ensure that DRG afferent projections are ensheathed after pioneer axons complete their navigation, which promotes efficient somatosensory neural function.
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Cody J
authors.initials: CJ
authors.lastname: Smith
authors.affiliation: Neuroscience Graduate Program, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Michael A
authors.identifier: 0000-0002-0689-6384
authors.initials: MA
authors.lastname: Wheeler
authors.affiliation: Department of Cell Biology, Duke University, Durham, North Carolina, United States of America.
authors.forename: Lindsay
authors.identifier: 0000-0002-4422-6963
authors.initials: L
authors.lastname: Marjoram
authors.affiliation: Department of Cell Biology, Duke University, Durham, North Carolina, United States of America.
authors.forename: Michel
authors.initials: M
authors.lastname: Bagnat
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, Virginia, United States of America.|Neuroscience Graduate Program, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Deppmann
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, Virginia, United States of America.|Neuroscience Graduate Program, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Sarah
authors.identifier: 0000-0002-1950-751X
authors.initials: S
authors.lastname: Kucenas
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001369:Axons / Q000378:metabolism; D002490:Central Nervous System / Q000254:growth & development / Q000378:metabolism; D005727:Ganglia, Spinal; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism; D017933:Peripheral Nervous System / Q000254:growth & development / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction; D013116:Spinal Cord / Q000254:growth & development / Q000378:metabolism; D013126:Spinal Nerve Roots / Q000254:growth & development / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics*; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development
chemical_list: D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha