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Role of DSCAM in netrin-1 mediated axon repulsion and neuronal migration

Purohit, Anish A.

Abstract Details

2011, Master of Science, University of Toledo, Biology (Cell-Molecular Biology).
Axon pathfinding and neuronal migration are key events for proper nervous system development and function. Neuronal growth cones explore the environment for extracellular cues, which guide the axons along specific paths towards their targets. Netrin-1, a bifunctional guidance cue, binds to receptors deleted in colorectal cancer (DCC) and Down syndrome cell adhesion molecule (DSCAM) mediating axon attraction, and uncoordinated-5 (UNC5) mediating axon repulsion. The DCC/UNC5 heterodimer also modulates netrin-1 repulsion in the developing nervous system. We found that DSCAM interacts with UNC5C and netrin-1 stimulation increases this interaction in postnatal cerebellar cells. Therefore, we hypothesize that DSCAM may play a role in netrin-1 repulsion. Here we show that in an in vitro growth cone collapse assay, netrin-1 induces mouse cerebellum external granule layer (EGL) cell growth cone collapse. The DSCAM intracellular domain modulates netrin-1 induced axon repulsion. Inhibiting DSCAM intracellular signaling causes aberrant neuronal migration in the postnatal cerebellar EGL cells ex vivo. Thus, DSCAM plays a critical role in netrin-1 repulsion.
Guofa Liu, MD/PhD (Advisor)
Richard Komuniecki, PhD (Committee Member)
Robert Steven, PhD (Committee Member)
Malathi Krishnamurthy, PhD (Committee Member)
Scott Leisner, PhD (Committee Member)
66 p.

Recommended Citations

Citations

  • Purohit, A. A. (2011). Role of DSCAM in netrin-1 mediated axon repulsion and neuronal migration [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1310173299

    APA Style (7th edition)

  • Purohit, Anish. Role of DSCAM in netrin-1 mediated axon repulsion and neuronal migration. 2011. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=toledo1310173299.

    MLA Style (8th edition)

  • Purohit, Anish. "Role of DSCAM in netrin-1 mediated axon repulsion and neuronal migration." Master's thesis, University of Toledo, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1310173299

    Chicago Manual of Style (17th edition)