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The Journal of Neuroscience, January 1, 2002, 22(1):248-256

The Tripotential Glial-Restricted Precursor (GRP) Cell and Glial Development in the Spinal Cord: Generation of Bipotential Oligodendrocyte-Type-2 Astrocyte Progenitor Cells and Dorsal-Ventral Differences in GRP Cell Function

Ninel Gregori^{1, *}, Christoph Pröschel^{2, *}, Mark Noble², and Margot Mayer-Pröschel²

¹ University of Utah School of Medicine, Salt Lake City, Utah 84132, and ² Center for Cancer Biology, University of Rochester Medical Center, Rochester, New York 14642

We have found that the tripotential glial-restricted precursor (GRP) cell of the embryonic rat spinal cord can give rise in vitro to bipotential cells that express defining characteristics of oligodendrocyte-type-2 astrocyte progenitor cells (O2A/OPCs). Generation of O2A/OPCs is regulated by environmental signals and is promoted by platelet-derived growth factor (PDGF), thyroid hormone (TH) and astrocyte-conditioned medium. In contrast to multiple observations indicating that oligodendrocyte precursor cells in the embryonic day 14 (E14) spinal cord are ventrally restricted, GRP cells are already present in both the dorsal and ventral spinal cord at E13.5. Ventral-derived GRP cells, however, were more likely to generate O2A/OPCs and/or oligodendrocytes than were their dorsal counterparts when exposed to TH, PDGF, or even bone morphogenetic protein-4. The simplest explanation of our results is that oligodendrocyte generation occurs as a result of generation of GRP cells from totipotent neuroepithelial stem cells, of O2A/OPCs from GRP cells and, finally, of oligodendrocytes from O2A/OPCs. In this respect, the responsiveness of GRP cells to modulators of this process may represent a central control point in the initiation of this critical developmental sequence. Our findings provide an integration between the earliest known glial precursors and the well-studied O2A/OPCs while opening up new questions concerning the intricate spatial and temporal regulation of precursor cell differentiation in the CNS.

Key words: glial-restricted precursor cell; GRP cell; oligodendrocyte; O2A progenitor cell; OPCs; spinal cord development; ventral origin; neuroepithelial stem cells

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^* N.G. and C.P. contributed equally to this manuscript.

Correspondence should be addressed to Margot Mayer-Pröschel, Center for Cancer Biology, Kornberg Medical Research Building, 601 Elmwood Avenue, Box 633, University of Rochester, Rochester, NY 14642. E-mail: margot_mayer-proschel{at}urmc.rochester.edu.

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Copyright © 2002 Society for Neuroscience  0270-6474/02/221248-09$05.00/0

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