Jab1 Affects Hair Cell Development in the Zebrafish Inner Ear
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Authors
Weber, Loren J.
Issue Date
2013
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Development of mechanosensory hair cells within the vertebrate inner ear is
crucial to a functioning auditory and vestibular (position and balance) system. By
investigating the underlying mechanisms and pathways through which hair cells
develop in the embryo, potential therapeutic avenues for hearing loss could be
explored. In addition to the development of hair cells, the formation of the
statoacoustic ganglion (SAG), the main nerve that innervates the inner ear and relays
sensory information to the brain, is fundamentally important. Cytokines have been
shown to play a key role in development, and many of the cytokines involved in the
development of hair cells are also involved in SAG development. One such cytokine
is macrophage migration inhibitory factor (MIF). MIF has been shown in past studies
to have an effect on both the developing auditory and nervous systems in multiple
models, including zebrafish. One binding partner of MIF is c-jun activation binding
protein (Jab1), which, through multiple downstream effectors, has various roles in the
embryo. In this study, we performed injection and electroporation of Jab1 start codon
morpholinos (antisense oligonucleotide designed to knock down gene expression)
directly into the inner ear of zebrafish embryos. Jab1 start codon MOs were shown to
decrease hair cells, while having little to no effect on the SAG. Additionally, a coinjection
of Jab I start codon and MIF MOs were shown to have a rescue effect in the
inner ear, as hair cell counts returned to that of controls. Future work should focus on
Jab1's multiple downstream effectors to uncover the mechanism by which hair cells
develop, as well delve deeper into the rescue effect of Jab1 and MIF MOs in order to
discover new therapeutics for mammalian hearing loss.
Description
vi, 51 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.