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
Gregori1, *,
Christoph
Pröschel2, *,
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
*
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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