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.
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Acknowledgements
We thank F. Gage (Salk Institute) and J. Goldman (Columbia University) for the gift of pNIT-GFP and dS-Red retrovirus and D. Rowitch (University of California San Francisco) for the gift of antibodies to Olig2. We thank T. Hawley for assistance with FACS sorting. We are particularly grateful to J. Corbin for discussion. This work was supported by US National Institutes of Health grants R01NS045702 and R01NS056427 to V.G., K99NS057944 to A.A., R01NS047344 and R01AG024984 to H.S. and R01NS048271 to G.M. and by the Hungarian National Office for Research and Technology GVOP-3.1.1.-2004-05-0230-/3.0 to G.S. and US National Institutes of Health Intellectual and Developmental Disabilities Research Center P30HD40677 to V.G.
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B.J. and A.A. designed, performed and analyzed all of the experiments. M.R. performed some of the in vivo experiments, cell imaging and cell counting. G.S. generated and provided the GAD65-GFP mice. Y.K., K.A.S., G.M. and H.S. generated and provided the Dcx-CreERT2 mice. V.G. designed the experiments with B.J. and A.A., supervised the project and wrote the manuscript with input from B.J.
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Jablonska, B., Aguirre, A., Raymond, M. et al. Chordin-induced lineage plasticity of adult SVZ neuroblasts after demyelination. Nat Neurosci 13, 541–550 (2010). https://doi.org/10.1038/nn.2536
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DOI: https://doi.org/10.1038/nn.2536
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