title: Chordin-induced lineage plasticity of adult SVZ neuroblasts after demyelination.
abstract: The mechanisms that regulate the developmental potential of adult neural progenitor populations under physiological and pathological conditions remain poorly defined. Glutamic acid decarboxylase 65 (GAD65)- and Doublecortin (Dcx)-expressing cells constitute major progenitor populations in the adult mouse subventricular zone (SVZ). Under normal physiological conditions, SVZ-derived GAD65-positive and Dcx-positive cells expressed the transcription factor Pax6 and migrated along the rostral migratory stream to the olfactory bulb to generate interneurons. After lysolecithin-induced demyelination of corpus callosum, however, these cells altered their molecular and cellular properties and migratory path. Demyelination upregulated chordin in the SVZ, which redirected GAD65-positive and Dcx-positive progenitors from neuronal to glial fates, generating new oligodendrocytes in the corpus callosum. Our findings suggest that the lineage plasticity of SVZ progenitor cells could be a potential therapeutic strategy for diseased or injured brain.
authors.affiliation: Center for Neuroscience Research, Children's National Medical Center, Washington, DC, USA.
authors.forename: Beata
authors.initials: B
authors.lastname: Jablonska
authors.affiliation: Center for Neuroscience Research, Children's National Medical Center, Washington, DC, USA.
authors.forename: Adan
authors.initials: A
authors.lastname: Aguirre
authors.affiliation: Center for Neuroscience Research, Children's National Medical Center, Washington, DC, USA.|George Washington University, Institute for Biomedical Sciences, Washington, DC, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Raymond
authors.affiliation: Department of Gene Technology and Developmental Neurobiology, Institute of Experimental Medicine, Budapest, Hungary.
authors.forename: Gabor
authors.initials: G
authors.lastname: Szabo
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Kitabatake
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Kurt A
authors.initials: KA
authors.lastname: Sailor
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Guo-Li
authors.initials: GL
authors.lastname: Ming
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Song
authors.affiliation: Center for Neuroscience Research, Children's National Medical Center, Washington, DC, USA.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Gallo
mesh_terms: D053687:Adult Stem Cells / Q000187:drug effects*; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D019070:Cell Lineage / Q000187:drug effects* / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects; D002552:Cerebral Ventricles / Q000473:pathology*; D003337:Corpus Callosum / Q000166:cytology; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005786:Gene Expression Regulation / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000235:genetics; D006023:Glycoproteins / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008244:Lysophosphatidylcholines; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics; D004676:Myelin Basic Protein / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009479:Neuropeptides / Q000235:genetics; D009836:Oligodendroglia / Q000187:drug effects / Q000502:physiology
chemical_list: C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D008244:Lysophosphatidylcholines; D008869:Microtubule-Associated Proteins; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D049452:Green Fluorescent Proteins; C054234:chordin; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2; D001973:Bromodeoxyuridine