Zebrafish as a Future Model for the Study of Human Chordomas Public
Errico, Kristen Nicole (2014)
Published
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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