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Cortical development depends on the active integration of cell-autonomous and extrinsic cues, but the coordination of these processes is poorly understood. Here, we show that the apical complex protein Pals1 and Pten have opposing roles in localizing the Igf1R to the apical, ventricular domain of cerebral cortical progenitor cells. We found that the(More)
Metabolic insult results in apoptosis and depletion of mature oligodendrocytes during demyelination. To examine the role of insulin-like growth factor-1 (IGF-1) during acute demyelination and remyelination in the adult CNS, we exposed transgenic mice that continuously express IGF-1 (IGF-1 tg) to cuprizone intoxication. Demyelination was observed within the(More)
To study the effects and mechanisms of insulin-like growth factor I (IGF-I) on brain myelination in vivo, the morphology of myelinated axons and the expression of myelin specific protein genes have been examined in transgenic (Tg) mice that overexpress IGF-I and that those ectopically express IGF binding protein-1 (IGFBP-1), a protein that inhibits IGF-I(More)
In studies of transgenic (Tg) mice that overexpress insulin-like growth factor-I (IGF-I) exclusively in the CNS, we demonstrated a dramatic increase in cerebellar granule cell number that appeared to be attributable predominantly to enhanced survival. IGF-I anti-apoptotic actions are well established in cultured neurons, but comparable studies in vivo are(More)
Insulin-like growth factor-I (IGF-I) has been shown to be a potent agent in promoting the growth and differentiation of oligodendrocyte precursors, and in stimulating myelination during development and following injury. To definitively determine whether IGF-I acts directly on the cells of oligodendrocyte lineage, we generated lines of mice in which the type(More)
Insulin-like growth factor-I (IGF-I) is widely expressed in the central nervous system (CNS). Whereas during normal development IGF-I is expressed predominantly by neurons and to a much lesser degree by glial cells, its expression in astrocytes, and often in microglia, is increased during and/or after variety of CNS injuries. Recently we have generated a(More)
Despite recent advances in our understanding of lineage of oligodendrocytes, detailed molecular characterization of this lineage in vivo is limited, primarily because of our inability to obtain a pure population of cells in situ. To define the molecular characteristics of oligodendrocyte lineage cells during development and their response to injury, we(More)
The in vivo actions of insulin-like growth factor-I (IGF-I) on cerebellum development have been investigated in transgenic (Tg) mice (IGF-II/I Tg mice) in whom an IGF-II promoter-driven IGF-I transgene is highly expressed in cerebellum. Compared to normal littermates, the brains of IGF-II/I Tg mice exhibited overgrowth beginning from the second week of(More)
Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, has been implicated in the pathogenesis of several disorders and injuries in the central nervous system (CNS). Unlike IGF-I, which promotes CNS growth, TNF-alpha causes brain growth retardation and neural damage. Recently TNF-alpha has been shown to inhibit IGF-I signaling and actions in(More)
Evidence suggests that interferon-gamma (IFN-gamma), a proinflammatory cytokine secreted by activated T lymphocytes, contributes a deleterious effect to immune-mediated demyelinating disorders such as multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Nevertheless, mouse strains that are normally resistant to EAE induction become(More)