title: The astrocyte/meningeal cell interface is a barrier to neurite outgrowth which can be overcome by manipulation of inhibitory molecules or axonal signalling pathways.
abstract: Invading meningeal cells form a barrier to axon regeneration after damage to the spinal cord and other parts of the CNS, axons stopping at the interface between meningeal cells and astrocytes. Axon behavior was examined using an in vitro model of astrocyte/meningeal cell interfaces, created by plating aggregates of astrocytes and meningeal cells onto coverslips. At these interfaces growth of dorsal root ganglion axons attempting to grow from astrocytes to meningeal cells was blocked, but axons grew rapidly from meningeal cells onto astrocytes. Meningeal cells were examined for expression of axon growth inhibitory molecules, and found to express NG2, versican, and semaphorins 3A and 3C. Astrocytes express growth promoting molecules, including N-Cadherin, laminin, fibronectin, and tenascin-C. We treated cultures in various ways to attempt to promote axon growth across the inhibitory boundaries. Blockade of NG2 with antibody and blockade of neuropilin 2 but not neuropilin 1 both promoted axon growth from astrocytes to meningeal cells. Blockade of permissive molecules on astrocytes with N-Cadherin blocking peptide or anti beta-1 integrin had no effect. Manipulation of axonal signalling pathways also increased axon growth from astrocytes to meningeal cells. Increasing cAMP levels and inactivation of rho were both effective when the cultures were fixed in paraformaldehyde, demonstrating that their effect is on axons and not via effects on the glial cells.
authors.affiliation: Department of Physiology and Cambridge Centre for Brain Repair, University of Cambridge, Cambridge CB2 3EG, England, UK.
authors.forename: Morven C
authors.initials: MC
authors.lastname: Shearer
authors.forename: Simone P
authors.initials: SP
authors.lastname: Niclou
authors.forename: David
authors.initials: D
authors.lastname: Brown
authors.forename: Richard A
authors.initials: RA
authors.lastname: Asher
authors.forename: Anthony J G D
authors.initials: AJ
authors.lastname: Holtmaat
authors.forename: Joel M
authors.initials: JM
authors.lastname: Levine
authors.forename: Joost
authors.initials: J
authors.lastname: Verhaagen
authors.forename: James W
authors.initials: JW
authors.lastname: Fawcett
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D006131:Growth Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D008578:Meninges / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D006131:Growth Inhibitors; D020933:Neurotrophin 3