Chordin-induced lineage plasticity of adult SVZ neuroblasts after demyelination.
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.
Jablonska
Beata
B
Center for Neuroscience Research, Children's National Medical Center, Washington, DC, USA.
Aguirre
Adan
A
Center for Neuroscience Research, Children's National Medical Center, Washington, DC, USA.
Raymond
Matthew
M
Center for Neuroscience Research, Children's National Medical Center, Washington, DC, USA.|George Washington University, Institute for Biomedical Sciences, Washington, DC, USA.
Szabo
Gabor
G
Department of Gene Technology and Developmental Neurobiology, Institute of Experimental Medicine, Budapest, Hungary.
Kitabatake
Yasuji
Y
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Sailor
Kurt A
KA
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Ming
Guo-Li
GL
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Song
Hongjun
H
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Gallo
Vittorio
V
Center for Neuroscience Research, Children's National Medical Center, Washington, DC, USA.
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
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