Jab1 Affects Hair Cell Development in the Zebrafish Inner Ear
Weber, Loren J.
MetadataShow full item record
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.