title: Tissue-type plasminogen activator exerts EGF-like chemokinetic effects on oligodendrocytes in white matter (re)myelination.
abstract: The ability of oligodendrocyte progenitor cells (OPCs) to give raise to myelin forming cells during developmental myelination, normal adult physiology and post-lesion remyelination in white matter depends on factors which govern their proliferation, migration and differentiation. Tissue plasminogen activator (tPA) is a serine protease expressed in the central nervous system (CNS), where it regulates cell fate. In particular, tPA has been reported to protect oligodendrocytes from apoptosis and to facilitate the migration of neurons. Here, we investigated whether tPA can also participate in the migration of OPCs during CNS development and during remyelination after focal white matter lesion.
  
  
  
  OPC migration was estimated by immunohistological analysis in spinal cord and corpus callosum during development in mice embryos (E13 to P0) and after white matter lesion induced by the stereotactic injection of lysolecithin in adult mice (1 to 21 days post injection). Migration was compared in these conditions between wild type and tPA knock-out animals. The action of tPA was further investigated in an in vitro chemokinesis assay.
  
  
  
  OPC migration along vessels is delayed in tPA knock-out mice during development and during remyelination. tPA enhances OPC migration via an effect dependent on the activation of epidermal growth factor receptor.
  
  
  
  Endogenous tPA facilitates the migration of OPCs during development and during remyelination after white matter lesion by the virtue of its epidermal growth factor-like domain.
authors.affiliation: Normandie Univ, UNICAEN, INSERM U1237, Physiology and imaging of neurological disorders (PhIND), Cyceron, Caen, 14000, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Leonetti
authors.affiliation: Normandie Univ, UNICAEN, INSERM U1237, Physiology and imaging of neurological disorders (PhIND), Cyceron, Caen, 14000, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Macrez
authors.affiliation: Normandie Univ, UNICAEN, INSERM U1237, Physiology and imaging of neurological disorders (PhIND), Cyceron, Caen, 14000, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Pruvost
authors.affiliation: Normandie Univ, UNICAEN, INSERM U1237, Physiology and imaging of neurological disorders (PhIND), Cyceron, Caen, 14000, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Hommet
authors.affiliation: Normandie Univ, UNICAEN, INSERM U1237, Physiology and imaging of neurological disorders (PhIND), Cyceron, Caen, 14000, France.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Bronsard
authors.affiliation: Normandie Univ, UNICAEN, INSERM U1237, Physiology and imaging of neurological disorders (PhIND), Cyceron, Caen, 14000, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Fournier
authors.affiliation: Normandie Univ, UNICAEN, INSERM U1237, Physiology and imaging of neurological disorders (PhIND), Cyceron, Caen, 14000, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Perrigault
authors.affiliation: Grupo de Neurobiología del Desarrollo-GNDe, Hospital Nacional de Parapléjicos-SESCAM, Toledo, Spain.|Grupo de Neuroinmuno-reparación, Hospital Nacional de Parapléjicos, Toledo, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Machin
authors.affiliation: Normandie Univ, UNICAEN, INSERM U1237, Physiology and imaging of neurological disorders (PhIND), Cyceron, Caen, 14000, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Vivien
authors.affiliation: Grupo de Neurobiología del Desarrollo-GNDe, Hospital Nacional de Parapléjicos-SESCAM, Toledo, Spain.|Grupo de Neuroinmuno-reparación, Hospital Nacional de Parapléjicos, Toledo, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Clemente
authors.affiliation: Grupo de Neurobiología del Desarrollo-GNDe, Hospital Nacional de Parapléjicos-SESCAM, Toledo, Spain.|Grupo de Neurobiología del Desarrollo (GNDe), Instituto Cajal, CSIC, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: De Castro
authors.affiliation: Normandie Univ, UNICAEN, INSERM U1237, Physiology and imaging of neurological disorders (PhIND), Cyceron, Caen, 14000, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Maubert
authors.affiliation: Normandie Univ, UNICAEN, INSERM U1237, Physiology and imaging of neurological disorders (PhIND), Cyceron, Caen, 14000, France. docagne@cyceron.fr.|Inserm, Centre Cyceron, Bvd Becquerel, BP5229, Caen Cedex, 14074, France. docagne@cyceron.fr.
authors.forename: Fabian
authors.initials: F
authors.lastname: Docagne
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects / Q000254:growth & development*; D003337:Corpus Callosum / Q000187:drug effects / Q000473:pathology; D004622:Embryo, Mammalian; D004815:Epidermal Growth Factor; D021621:Imaging, Three-Dimensional; D015151:Immunoblotting; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000187:drug effects; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects*; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*; D066127:White Matter / Q000187:drug effects
chemical_list: D004815:Epidermal Growth Factor; D010959:Tissue Plasminogen Activator
keywords: Development; Endothelial cells; Epidermal growth factor; Lysolecithin; Multiple sclerosis; Myelin; Spinal cord; Vasophilic migration