title: [Krox20 inactivation in the PNS leads to CNS/PNS boundary transgression by central glia].
abstract: CNS/PNS interfaces constitute cell boundaries, defining territories with different neuronal and glial contents. Despite their potential implications for regenerative medicine, the mechanisms that restrict oligodendrocytes and astrocytes to the CNS and Schwann cells to the PNS are not known in mammals. To investigate the involvement of peripheral glia and myelin in CNS/PNS boundary maintenance, we first studied mutant mice. We found that inactivation of Krox20/Egr2, a master regulatory gene for myelination in Schwann cells, resulted in CNS/PNS boundary transgression by astrocytes and oligodendrocytes, and in myelination of nerve root axons by oligodendrocytes. In contrast, no such migration was observed in mice with the Trembler(J) mutation, which prevents PNS myelination without affecting Krox20 expression. These findings suggest that CNS/PNS boundary maintenance requires a new Krox20 function independent of myelination control. We also examined a patient with congenital amyelinating neuropathy, whose Schwann cells lack KROX20 protein. Interestingly, the patient's nerve roots were also invaded by oligodendrocytes and astrocytes, indicating that CNS/PNS boundary transgression by central glia can occur in human pathological situations and that the underlying mechanisms are the same as in mutant mice.
authors.affiliation: INSERM, U1024, CNRS UMR 8197, Ecole Normale Supérieure, Plate-forme Transcriptome, IBENS, 46 rue d'Ulm, 75230 Paris Cédex 05, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Charnay
authors.forename: Fanny
authors.initials: F
authors.lastname: Coulpier
authors.forename: Laurence
authors.initials: L
authors.lastname: Decker
authors.forename: Benoît
authors.initials: B
authors.lastname: Funalot
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Vallat
authors.forename: Federico
authors.initials: F
authors.lastname: Garcia-Bragado
authors.forename: Piotr
authors.initials: P
authors.lastname: Topilko
mesh_terms: D002490:Central Nervous System / Q000502:physiology*; D051767:Early Growth Response Protein 2 / Q000502:physiology*; D006801:Humans; D017933:Peripheral Nervous System / Q000502:physiology*
chemical_list: C497326:EGR2 protein, human; D051767:Early Growth Response Protein 2