Work

Perturbations in Oligodendrocyte Progenitor Growth and Differentiation: Neurofibromin and Fgf2 Signaling

Year: 2004

Type: article

Abstract: The study of oligodendrogenesis and of stem cells in general has become a burgeoning field in recent years.The ability to replace specific cells of the body as things begin to go awry, to lessen the suffering of humanity is the holy grail in the eyes of many researchers.In order to successfully manipulate endogenous or cultured stem cells or more restricted precursors to replace those damaged in disease required specific knowledge of the complexities of developmental influences.Many factors influencing the specification and fate of oligodendrocyte progenitors have been discovered in recent years, but what links the various pathways is largely unknown.Some factors, including platelet-derived growth factor (PDGF) and basic fibroblast growth factor (FGF2), are involved at many stages of oligodendrocyte development.We chose to utilize a mouse model of neurofibromatosis type 1 (NF1) to study the influence of neurofibromin and ras signaling on oligodendrocyte development.Patients with NF1 exhibit a broad spectrum of CNS abnormalities that altered glia could play a part in.In our first study we demonstrate increased numbers of oligodendrocyte progenitor cells (OPCs) in vivo and in vitro embryonically and in adult mice.The accumulation of OPCs in vitro results in part from a farnesyl-transferase inhibitor (FTI; an H-ras inhibitor) -sensitive FGF2hypersensitivity.This is the first linking of neurofibromin and ras signaling to FGF2 hypersensitivity.In our second study we begin to focus on the ability of Nf1 mutant OPCs to differentiate normally.Nf1 mutant cells have an FTI-sensitive tendency to abnormally coexpress GalC and GFAP, markers of oligodendrocytes and astrocytes respectively.We also begin to explore a link between Nf1 mutation and increased activation of another factor that influences oligodendrocyte development, Notch-1.

Source: OhioLink ETD Center (Ohio Library and Information Network)

Author: Michael Bennett

Institution: University of Cincinnati

Language: English

Topic: Neurogenesis and neuroplasticity mechanisms

Subfield: Developmental Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Multiple Sclerosis Society, Multiple Sclerosis Society, National Institutes of Health, Directorate for Biological Sciences, National Institute of Child Health and Human Development

OpenAlex ID: W2513190391

FWCI:

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