• Login
    View Item 
    •   DSpace Home
    • Stony Brook University
    • Stony Brook Theses & Dissertations [SBU]
    • View Item
    •   DSpace Home
    • Stony Brook University
    • Stony Brook Theses & Dissertations [SBU]
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of DSpaceCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsDepartmentThis CollectionBy Issue DateAuthorsTitlesSubjectsDepartment

    My Account

    LoginRegister

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Helping to Start and Stop Myelination: Csk has Dual Regulatory Functions during Oligodendrocyte Development

    Thumbnail
    View/Open
    Tzvetanova_grad.sunysb_0771E_10365.pdf (194.5Mb)
    Date
    1-Dec-11
    Author
    Tzvetanova, Iva Dimitrova
    Publisher
    The Graduate School, Stony Brook University: Stony Brook, NY.
    Metadata
    Show full item record
    Abstract
    The ability of oligodendrocyte progenitors (OPCs) to generate sufficient numbers of myelinating oligodendrocytes is critical both for developmental myelination and for repair following demyelination. The timing and location of gliogenesis are tightly controlled but the molecular mechanisms that underlie this control are poorly understood. Here I report that the C-terminal Src Kinase (Csk) acts as a molecular switch for Src Family Kinase activity in oligodendrocytes, with distinct and opposing roles for Csk in early versus late stages of development. Early in development Csk is critical for the appropriate onset of oligodendrocyte progenitor differentiation. Csk suppresses OPC proliferation such that Csk depletion in OPCs in vitro and in vivo led to proliferation under conditions that normally promoted cell cycle exit. Hyperproliferation of Csk-deficient OPCs resulted in delayed oligodendrocyte maturation accompanied by delayed myelination onset, while survival of newly-formed oligodendrocytes was increased. These data suggest that, during myelination onset, Csk is a pro-differentiation factor that promotes timely OPC cell cycle exit. Adult Csk null mice, however, developed hypermyelination, suggesting that Csk also contributes to myelination arrest. Thus, Csk deletion caused increased levels of myelin basic protein as well as increased myelination in the cortex, cerebellum and spinal cord, although there was no change in the number of mature oligodendrocytes. Further analysis of myelin ultrastructure using transmission electron microscopy revealed increased numbers of myelin wraps such that the g-ratio was significantly decreased. To address a putative role for Csk during myelin repair I evaluated the response of Csk null mice to cuprizone-induced demyelination. Preliminary analyses reveal that during remyelination Csk mutant animals exhibit increased numbers of OPCs and mature oligodendrocytes, increased myelin content, and lower g-ratio as well as decreased axonal degeneration. I, therefore, propose that Csk is a novel regulator of oligodendrocyte development with two distinct roles: generating appropriate numbers of oligodendrocytes at the onset of myelination, and terminating wrapping during myelination.
    URI
    http://hdl.handle.net/1951/56142
    Collections
    • Stony Brook Theses & Dissertations [SBU] [1955]

    SUNY Digital Repository Support
    DSpace software copyright © 2002-2023  DuraSpace
    Contact Us | Send Feedback
    DSpace Express is a service operated by 
    Atmire NV
     

     


    SUNY Digital Repository Support
    DSpace software copyright © 2002-2023  DuraSpace
    Contact Us | Send Feedback
    DSpace Express is a service operated by 
    Atmire NV