title: Investigation of the proteolipid protein promoter activity during demyelination and repair.
abstract: The transgenic plp-GFP mouse line expressing the green fluorescent protein (GFP) driven by the mouse myelin proteolipid protein (plp) gene promoter has been previously used to study the contribution of the plp lineage to oligodendrocyte development in the embryonic brain. Here, we show that the GFP fluorescence reflects the developmental expression of proteolipid protein during the postnatal development until adulthood in brain slices and in primary cultures of plp-GFP(+) cells derived from postnatal animals. In the adult brain, plp-GFP-expressing cells are mature oligodendrocytes but not oligodendroglial progenitors. In the model of focal demyelination induced by lysolecithin (LPC) in the corpus callosum of adult plp-GFP animals, we observed an up-regulation of the morphogen Sonic Hedgehog (Shh) in the LPC-induced lesion but not in the control animals. Moreover, we show that the adenovirus-mediated transfer of Shh in the lesion results in the attenuation of the demyelination extent as evidenced by GFP fluorescence analysis in Shh-treated and control animals. Altogether these data show how plp-GFP fluorescence can be monitored to follow the oligodendrocyte lineage during demyelination and identify Shh morphogen as an important factor during repair.
authors.affiliation: Laboratory of Neurobiology and Development, CNRS, UPR-3294, Institute of Neurobiology Alfred Fessard IFR2118, Signal Transduction and Developmental Neuropharmacology Team, Gif-sur-Yvette 91198, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Ferent
authors.forename: Martial
authors.initials: M
authors.lastname: Ruat
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Traiffort
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D003711:Demyelinating Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018991:Myelin Proteolipid Protein / Q000378:metabolism*; D009186:Myelin Sheath / Q000473:pathology*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D018991:Myelin Proteolipid Protein; D049452:Green Fluorescent Proteins
keywords: Glia; Green fluorescent protein; Oligodendrocytes; Sonic Hedgehog; Stem cells