| Glial progenitors of the central nervous system include oligodendroglial progenitors (OPCs) and subsets of astrocytes that express glial fibrillary acidic protein (GFAP). Together, these cells constitute the known sources for replacement of cell loss due to injury or disease in the mammalian central nervous system (CNS). In recent years, it has become clear that radial glia, the Nestin+/Sox2+ radially arranged astrocytes of the developing neural tube, are the progenitor cells responsible for generating CNS neurons and microglia during development. This dissertation includes studies which describe glial progenitor biology under the different contexts of postnatal development and adult inflammation, including the discovery that radially-arranged, Nestin+/Sox2+ astrocytes in the adult spinal cord under inflammatory conditions demonstrate properties similar to their radial glial forbears.;Chapter 1 is an introduction to the work described in this dissertation. Reviews of stem cell biology, regenerative medicine, radial glial biology and its relationship to neurogenesis during development, as well as neurovascular biology, adult neuronogenesis, polydendrocytes and the neuroinflammatory glial response are given brief treatment as a primer for understanding the dissertation projects. A brief summary of dissertation findings concludes Chapter 1.;Chapter 2 covers novel aspects of OPC contribution to both early and late postnatal development. Specifically, proteolipid-promoter-expressing polydendrocytes (PPEPs), a subset of OPCs, are tri-potent during early postnatal development, giving rise to mature oligodendrocytes, astrocytes, and GABA-ergic interneurons, while in late postnatal development they generate pyramidal neurons in the adult piriform cortex.;Chapter 3 describes the discovery of a novel, cryptic, inflammation-inducible niche comprised of neurovascular astrocytes, which when activated under conditions of experimental autoimmune encephalomyelitis (EAE) are capable of generating more astrocytes, as well as many newborn neurons which survive long-term in the adult spinal cord.;Chapter 4 summarizes the main dissertation findings, the conclusions that have been drawn from them, as well as the contributions of each project to both basic science and clinical medicine. A survey of potential future directions to be taken in this field ends the discussion, with emphasis on questions that remain to be answered. |
