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EFFECTS OF LOSS OF NF1 GENE ON PERIPHERAL NERVOUS SYSTEM PROGENITORS AND TUMORIGENESIS

WILLIAMS, JON

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2008, PhD, University of Cincinnati, Medicine : Neuroscience/Medical Science Scholars Interdisiplinary.
This dissertation contains three independent studies involving the developmental cell biology of neural crest-derived glial lineage cells in the context of neurofibromatosis, type 1 (NF1). The first study (Chapter 2) addresses the growth factor requirements of peripheral nervous system progenitor cells in an effort to facilitate the characterization and amplification of such cells. We identified an expandable embryonic dorsal root ganglion progenitor population which is dependent on EGFR signaling, clonally expandable, multipotent, and capable of benign lesion formation in immunocompromised mice. This work was expanded to prospectively identify EGFR+; P75+ cells by FACS analysis of human neurofibromas, and we demonstrate that these human glial progenitor cells maintain the cellular phenotypes of EGFR-dependent growth, in vitro multi-lineage differentiation, and capacity to form tumors in vivo. Together, these findings suggest that the expansion of an EGFR-expressing early glial progenitor contributes to neurofibroma formation. The second study (Chapter 3) demonstrates the importance of the timing of Nf1 gene ablation specifically at the Schwann cell precursor stage for in vitro colony proliferation and in vivo tumor formation and pigmentation. The final study (Chapter 4) details the gene expression profiles of a tissue culture model of peripheral nerve tumorigenesis (Nf1-/- TXF cells) with emphasis on the similarities in this population with an early glial phenotype as well as dysregulation of various cell adhesion genes potentially involved in NF1 tumorigenesis. A general introduction (Chapter 1) and concluding discussion (Chapter 5) frame these findings within the literature to date and critically addresses the impact of our findings on the current understanding of the biology neurofibroma formation.
Nancy Ratner, PhD (Advisor)
Kuan Alex, MD, PhD (Committee Member)
Nakafuku Masato, MD, PhD (Committee Member)
Campbell Kenny, PhD (Committee Member)
Potter Steve, PhD (Committee Member)
175 p.

Recommended Citations

Citations

  • WILLIAMS, J. (2008). EFFECTS OF LOSS OF NF1 GENE ON PERIPHERAL NERVOUS SYSTEM PROGENITORS AND TUMORIGENESIS [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1212181112

    APA Style (7th edition)

  • WILLIAMS, JON. EFFECTS OF LOSS OF NF1 GENE ON PERIPHERAL NERVOUS SYSTEM PROGENITORS AND TUMORIGENESIS. 2008. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1212181112.

    MLA Style (8th edition)

  • WILLIAMS, JON. "EFFECTS OF LOSS OF NF1 GENE ON PERIPHERAL NERVOUS SYSTEM PROGENITORS AND TUMORIGENESIS." Doctoral dissertation, University of Cincinnati, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1212181112

    Chicago Manual of Style (17th edition)