Oligodendrocytes, the myelin forming cells of the CNS, develop from identified precursor cells known alternately as oligodendrocyte progenitor cells (OPCs), polydendrocytes, or NG2 cells. These cells appear about midgestation in rodents at specific locations within the developing CNS, migrate extensively, proliferate as they migrate, and then slowly differentiate into myelin-forming cells. Surprisingly, a large fraction of the OPC population fails to fully differentiate and persists throughout the adult CNS as a slowly dividing cell that can be considered an fourth glial cell type. The functions of these adult OPCs are not well understood, in part, because of their unusual mixture of glial and neuronal properties. Major questions remain regarding 1) the phenotypic plasticity of these cells in developing and adult animals and after injury and 2) the role of electrical excitability in OPC development and function. The goal of this proposal is to develop new viral-based tools for analyzing the development and properties of NG2+ OPCs. Our strategy takes advantage of the availability of cell-type specific inducible cre mouse driver lines and recently developed "flip" vectors in which tandem mutant loxP sites allow for inversion of selected genes from an anti-sense to sense orientation. This strategy allows for temporal control of the expression of marker antigens, functional proteins and RNAi. The tools to be developed here can be used widely to study other glial cell types within the central and peripheral nervous system.
Oligodendrocytes, the myelin-forming cells of the CNS, develop from an identified precursor cell that has an unusual mixture of neuronal and glial properties. Their functional role(s) in CNS homeostasis is unknown. The new tools to be developed here will help us to understand the unusual properties of these cells and how those properties relate to the responses of these cells to injury and demyelination.