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Investigating Neural Stem and Progenitor Cell Intracrine Signaling

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2019, Master of Arts, Ohio State University, Psychology.
In the adult mammalian brain, there are two regions where neural stem and progenitor cells reside and proliferate throughout life: the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampus. While much of the current research focuses on these cells’ ability to create new neurons, a process known as neurogenesis, new findings indicate that neural stem and progenitor cells (NSPCs) may influence their niches through the secretion of growth factors. Our previous work indicates that NSPCs express 1/3 of the vascular endothelial growth factor (VEGF) in the DG. While global VEGF has been shown to support the proliferation and maturation of adult-born DG neurons, the role of NSPC-derived VEGF is not entirely understood. Our data suggest that VEGF plays a role in regulating NSPC stemness in the DG. Currently, we aim to investigate the role of a VEGF/VEGFR2 intracellular autocrine (i.e. intracrine) signaling pathway in regulating NSPC stemness and maintenance. This thesis contributes to our ongoing work by investigating the immediate effects of VEGF knockdown on NSPC stemness in vitro and modeling VEGF knockdown to determine the NSPC-derived VEGF signaling pathway in vivo. My results suggest NSPC-derived VEGF knockdown increases NSPC proliferation, which is indicative of impaired stemness, in vitro. To investigate VEGF intracrine signaling in vivo we utilized a transgenic mouse line of inducible NSPC-derived VEGF knockdown was accompanied by EYFP reporter expression. I investigated the possible limitations of this commonly used genetic model and discovered recombination induced expression of one fluorescent reported does not accurately predict recombination of another gene at a single cell level. These data indicate that we may not accurately identify NSPC-derived VEGF intracrine signaling using our mouse model.
Elizabeth Kirby, Ph.D. (Advisor)
Kathryn Lenz, Ph.D. (Committee Member)
Jonathan Godbout, Ph.D. (Committee Member)
43 p.

Recommended Citations

Citations

  • Dause, T. (2019). Investigating Neural Stem and Progenitor Cell Intracrine Signaling [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1555618643450352

    APA Style (7th edition)

  • Dause, Tyler. Investigating Neural Stem and Progenitor Cell Intracrine Signaling. 2019. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1555618643450352.

    MLA Style (8th edition)

  • Dause, Tyler. "Investigating Neural Stem and Progenitor Cell Intracrine Signaling." Master's thesis, Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1555618643450352

    Chicago Manual of Style (17th edition)