The Cortical Ancestry of Oligodendrocytes: Common Principles and Novel Features

Studies on the development of cortical oligodendrocytes indicate that although general principles that apply to other parts of the CNS are applicable, there are important differences that appear to be critical to the analysis of this lineage in the cortex. Herein, we review previous studies demonstrating that oligodendrocyte-type-2 astrocyte progenitor cells (or oligodendrocyte precursor cells; aka O-2A/OPCs) of the developing postnatal cortex exhibit a striking cell-intrinsic bias towards undergoing prolonged self-renewal in the relative absence of oligodendrocyte generation [Power et al., Dev Biol 2002;245:362-375]. This phenotype is quite distinct from that observed in comparable cells isolated from the optic tract. This predilection for self-renewal is associated with a lessened response to inducers of oligodendrocyte generation and of possible mechanistic importance in regards to these other properties. We also review studies on stem/progenitor cells isolated from the embryonic cortex that are able to generate oligodendrocytes. As for the studies on O-2A/OPCs, important differences also distinguish these early cells from those studied in other CNS regions in their response to signaling molecules and expression of the Dlx family of transcriptional regulators [He et al., J Neurosci 2001;21:8854-8862; Yung et al., Proc Natl Acad Sci USA 2002;99:16273-16278]. We also present new data on clonal analysis of A2B5+ precursor cells isolated from the E13.5 cortex, demonstrating that this tissue appears to contain a cell similar in properties to the tripotential glial-restricted precursor cell that has been isolated from embryonic spinal cord [Rao et al., Proc Natl Acad Sci USA 1998;95:3996-4001]. Moreover, the A2B5+ precursor cells isolated from embryonic cortex are much more heterogeneous than is seen in the spinal cord at this age, even to the point of including an A2B5/PSA-NCAM double-positive cell that can generate neurons.