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Role of shox2 in zebrafish otic neuron development

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Project Abstract Hearing loss is a highly heterogeneous genetic disorder that makes diagnosis and treatment of patients challenging. Mutations in genes that result in syndromic hearing loss are often involved in the development of hair cells and auditory neurons. The discovery and study of genetic factors that contribute to the development of the inner ear will clarify the molecular etiology behind hearing loss and allow development of strategies to treat hearing loss. The short stature homeobox domain 2 (SHOX2) gene was identified as a candidate transcription factor involved in early development of auditory neuron through bioinformatic analysis. To better understand and recapitulate the role of human SHOX2 in inner ear development, zebrafish was chosen as a model organism. During embryonic development, zebrafish shox2 is expressed in the otic placode and later in the cranial ganglia which includes the statoacoustic neurons. I hypothesize that shox2 determines the cell fate of otic progenitors that give rise to neurons. I will evaluate auditory and vestibular behavior of zebrafish after morpholino knockdown of shox2. I will determine shox2 expression in otic progenitors by performing immunofluorescence in situ hybridization on zebrafish reporter lines that mark the otic progenitor pools. Furthermore, I will determine how shox2 knockdown affects the number of cells within each progenitor population. Finally, I will perform lineage tracing by generating and utilizing a tamoxifen inducible shox2-p2A?CreERT2 to mark progeny that arise from shox2 cells. These aims will clarify the role of shox2 in establishment of otic progenitor cells and potentially add this gene to a repertoire of factors responsible for hair cell and otic neuron development.
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