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

Abstract

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.

Hes1 but not Hes5 regulates an astrocyte versus oligodendrocyte fate choice in glial restricted precursors

“…We found that in AP-infected cells, approximately 16 Ϯ 2% were myelin proteolipid protein (PLP) -immunoreactive and 13 Ϯ 4% were GalCimmunoreactive 5 days after the cells were cultured in oligodendrocytepromoting conditions. These numbers are consistent with the extent of oligodendrocyte differentiation observed in other experiments (Rao et al, 1998;Gregori et al, 2002). In contrast, in Hes1-infected cells, there were very few PLP-or GalC-immunoreactive cells (Ͻ1%, Figs.…”

“…G3PDH (25 cycles) was used as a control. Herrera et al, 2001;Gregori et al, 2002). Our results suggest that Hes1 acts at the GRP stage to promote astrocyte differentiation.…”

“…1), which can generate both oligodendrocytes and astrocytes in vitro and in vivo (Rao et al, 1998;Herrera et al, 2001;Gregori et al, 2002). To determine whether Hes1 regulates glial differentiation of GRPs, a replication-incompetent retroviral construct containing a neomycin-resistant gene was used to overexpress Hes1.…”

Spatiotemporal gradient of oligodendrocyte differentiation in chick optic tectum requires brain integrity and cell‐cell interactions

“…Differentiation here occurred in the presence or absence of FBS. Development of tectal oligodendrocytes thus appears to be fundamentally different from mammalian oligodendrocytes arising under the scheme involving O-2A progenitor cells, where FBS inhibits their differentiation (Raff et al, 1983;Gregori et al, 2002).…”

PDGF α-Receptor Signal Strength Controls an RTK Rheostat That Integrates Phosphoinositol 3′-Kinase and Phospholipase Cγ Pathways during Oligodendrocyte Maturation

“…First, glial progenitors that can generate oligodendrocytes are present at E13 in dorsal spinal cord (Lee et al, 2000;Gregori et al, 2002), indicating that non-pMN foci also have at least the potential to generate oligodendrocytes. Second, PDGFR␣ expression may not be obligate for all oligodendrocyte progenitors, because a population of OPCs emerge from the olfactory anlage independent of PDGFR␣ (Spassky et al, 2001).…”