Zebrafish as a Future Model for the Study of Human Chordomas Open Access

Errico, Kristen Nicole (2014)

Permanent URL: https://etd.library.emory.edu/concern/etds/2f75r8608?locale=en
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Abstract

Chordomas are rare malignant bone tumors of the spine that arise during human development. Current treatment options are of limited success and overall prognosis is poor. Discovery of the ability to generate chordoma-like tumors in zebrafish embryos has shown promise for an in vivo model to study chordoma causes, formation, and treatment options by using zebrafish for high throughput drug screens. Characterization of the notochordal tumors in zebrafish is necessary to confirm that they are biologically representative of human chordomas. Using in situ analysis, we have attempted to determine when and where TGF-β2,3 and DRAKR1b1,10 are expressed in developing zebrafish embryos to better understand the mechanism for tumor formation and the characteristic features of the tumors. TGF- β is believed to play a role in tumor formation, as zebrafish tumor induction is dependent on a drug blocking TGF-ß receptors. DRAKR is believed to be analogous to the characteristic expression of AKR in chordomas. Due to unforeseen difficulties obtaining embryos to test in the laboratory, the limited data obtained is supplemented with a literature-based review of chordoma research. Research indicates that zebrafish remain a useful tool to study chordomas. With further characterization of chordoma-like tumors in zebrafish, we expect to discover possible novel drug targets including, but not limited to, TGF-β and AKR.

Table of Contents

Abstract ................................................................................................................................

Chapter 1............................................................................................................................ 1

Chordomas......................................................................................................................... 1

Notochord Background..................................................................................................... 2

The Misregulation of Brachyury as a Marker for Chordomas..................................... 3

The Misregulation of the mTOR Pathway...................................................................... 6

The Zebrafish Model System and Formation of Chordoma-Like Tumors.................. 8

Chapter 2............................................................................................................................ 9

Purpose............................................................................................................................... 9

Research Aim................................................................................................................... 11

Hypothesis........................................................................................................................ 14

Results.............................................................................................................................. 14

Materials and Methods................................................................................................... 18

Discussion........................................................................................................................ 19

References........................................................................................................................ 22

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