Abstract
After central nervous system (CNS) demyelination-such as occurs during multiple sclerosis-there is often spontaneous regeneration of myelin sheaths, mainly by oligodendrocytes but also by Schwann cells. The origins of the remyelinating cells have not previously been established. We have used Cre-lox fate mapping in transgenic mice to show that PDGFRA/NG2-expressing glia, a distributed population of stem/progenitor cells in the adult CNS, produce the remyelinating oligodendrocytes and almost all of the Schwann cells in chemically induced demyelinated lesions. In contrast, the great majority of reactive astrocytes in the vicinity of the lesions are derived from preexisting FGFR3-expressing cells, likely to be astrocytes. These data resolve a long-running debate about the origins of the main players in CNS remyelination and reveal a surprising capacity of CNS precursors to generate Schwann cells, which normally develop from the embryonic neural crest and are restricted to the peripheral nervous system.
Copyright 2010 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult Stem Cells / metabolism
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Adult Stem Cells / pathology
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Animals
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Astrocytes / metabolism
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Astrocytes / pathology
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Basic Helix-Loop-Helix Transcription Factors / biosynthesis
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Cells, Cultured
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Central Nervous System / drug effects
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Central Nervous System / pathology
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Central Nervous System / surgery
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Demyelinating Diseases / chemically induced
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Demyelinating Diseases / genetics
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Demyelinating Diseases / metabolism*
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Demyelinating Diseases / pathology
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Demyelinating Diseases / physiopathology
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Disease Models, Animal
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Female
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Integrases / genetics
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Lysophosphatidylcholines / administration & dosage
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Mice
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Mice, Transgenic
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Microscopy
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Multiple Sclerosis / genetics
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Multiple Sclerosis / metabolism*
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Multiple Sclerosis / pathology
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Multiple Sclerosis / physiopathology
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Nerve Regeneration*
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Nerve Tissue Proteins / biosynthesis
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Nerve Tissue Proteins / genetics
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Oligodendrocyte Transcription Factor 2
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Oligodendroglia / metabolism*
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Oligodendroglia / pathology
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Receptor, Fibroblast Growth Factor, Type 3 / biosynthesis
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Receptor, Fibroblast Growth Factor, Type 3 / genetics
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Receptor, Platelet-Derived Growth Factor alpha / biosynthesis
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Receptor, Platelet-Derived Growth Factor alpha / genetics
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Schwann Cells / metabolism*
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Schwann Cells / pathology
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Lysophosphatidylcholines
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Nerve Tissue Proteins
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Olig2 protein, mouse
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Oligodendrocyte Transcription Factor 2
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Fgfr3 protein, mouse
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Receptor, Fibroblast Growth Factor, Type 3
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Receptor, Platelet-Derived Growth Factor alpha
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Cre recombinase
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Integrases