Date of Completion

Spring 4-25-2024

Thesis Advisor(s)

Joseph LoTurco

Honors Major

Physiology and Neurobiology

Disciplines

Cancer Biology | Cell Biology | Developmental Neuroscience | Molecular and Cellular Neuroscience

Abstract

Supratentorial Ependymoma (ST-EPN) is a subtype of ependymoma, a primary solid tumor found throughout the nervous system. ST-EPN are most commonly caused by an oncogenic fusion between the zinc finger gene ZFTA and the RELA, and this distinct ependymoma subtype is readily modeled in mice by conditional expression of ZFTA-RELA in radial glial cells. ST-EPN are known to have a distinctive arrangement of tumor cells and vasculature forming pseudo-rosettes in which polarized tumor cells surround blood vessels within the tumors. It is not known how these pseudo-rosettes or the tumor vasculature form and develop in ST-EPN, so in this study we used a mouse model of ST-EPN to track the development of blood vessel growth into ST-EPN like tumors induced in mice. ZFTA-RELA was conditionally expressed in radial glial cells in neonates by postnatal electroporation of Cre-mRNA, and brains were sectioned and analyzed at postnatal days 14(P14), P21, and P30 to assess the formation of ST-EPN tumors and associated vasculature patterns. Results indicate marked changes in tumor vasculature density and area compared to tumor free regions, as well as the formation of tumor rosettes. We conclude that tumor cell vascular patterns typical of human EPN also form in mice, and this should allow for future experiments to explore the mechanisms by which ST-EPN tumor cells increase and alter vasculature growth in the developing brain.

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