title: Developmental Origin of Oligodendrocyte Lineage Cells Determines Response to Demyelination and Susceptibility to Age-Associated Functional Decline.
abstract: Oligodendrocyte progenitors (OPs) arise from distinct ventral and dorsal domains within the ventricular germinal zones of the embryonic CNS. The functional significance, if any, of these different populations is not known. Using dual-color reporter mice to distinguish ventrally and dorsally derived OPs, we show that, in response to focal demyelination of the young adult spinal cord or corpus callosum, dorsally derived OPs undergo enhanced proliferation, recruitment, and differentiation as compared with their ventral counterparts, making a proportionally larger contribution to remyelination. However, with increasing age (up to 13 months), the dorsally derived OPs become less able to differentiate into mature oligodendrocytes. Comparison of dorsally and ventrally derived OPs in culture revealed inherent differences in their migration and differentiation capacities. Therefore, the responsiveness of OPs to demyelination, their contribution to remyelination, and their susceptibility to age-associated functional decline are markedly dependent on their developmental site of origin in the developing neural tube.
authors.affiliation: Wellcome Trust-MRC Cambridge Stem Cell Institute and Department of Clinical Neurosciences, Clifford Allbutt Building, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0AH, UK.
authors.forename: Abbe H
authors.initials: AH
authors.lastname: Crawford
authors.affiliation: Wolfson Institute for Biomedical Research, University College London (UCL), Gower Street, London WC1E 6BT, UK.
authors.forename: Richa B
authors.initials: RB
authors.lastname: Tripathi
authors.affiliation: Wolfson Institute for Biomedical Research, University College London (UCL), Gower Street, London WC1E 6BT, UK. Electronic address: w.richardson@ucl.ac.uk.
authors.forename: William D
authors.initials: WD
authors.lastname: Richardson
authors.affiliation: Wellcome Trust-MRC Cambridge Stem Cell Institute and Department of Clinical Neurosciences, Clifford Allbutt Building, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0AH, UK. Electronic address: rjf1000@cam.ac.uk.
authors.forename: Robin J M
authors.initials: RJM
authors.lastname: Franklin
keywords: glial diversity; myelin; oligodendrocyte; oligodendrocyte progenitor; remyelination