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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult Stem Cells / drug effects*
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Animals
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Bromodeoxyuridine / metabolism
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Cell Count / methods
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Cell Differentiation / drug effects*
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Cell Differentiation / genetics
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Cell Lineage / drug effects*
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Cell Lineage / genetics
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Cell Movement / drug effects
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Cerebral Ventricles / pathology*
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Corpus Callosum / cytology
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Demyelinating Diseases / chemically induced
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Demyelinating Diseases / pathology*
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Doublecortin Domain Proteins
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Doublecortin Protein
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Gene Expression Regulation / drug effects
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Glutamate Decarboxylase / genetics
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Glycoproteins / pharmacology*
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Green Fluorescent Proteins / genetics
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Intercellular Signaling Peptides and Proteins / pharmacology*
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Lysophosphatidylcholines
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Mice
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Mice, Transgenic
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Microtubule-Associated Proteins / genetics
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Myelin Basic Protein / metabolism
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Nerve Tissue Proteins / metabolism
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Neurogenesis / drug effects
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Neurogenesis / genetics
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Neuronal Plasticity / drug effects
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Neurons / drug effects*
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Neurons / physiology
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Neuropeptides / genetics
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Oligodendroglia / drug effects
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Oligodendroglia / physiology
Substances
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Dcx protein, mouse
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Doublecortin Domain Proteins
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Doublecortin Protein
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Glycoproteins
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Intercellular Signaling Peptides and Proteins
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Lysophosphatidylcholines
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Microtubule-Associated Proteins
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Myelin Basic Protein
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Nerve Tissue Proteins
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Neuropeptides
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Green Fluorescent Proteins
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chordin
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Glutamate Decarboxylase
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glutamate decarboxylase 2
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Bromodeoxyuridine