Spatial Patterining in Zebrafish Inner Ear

About This Grant

PROJECT SUMMARY Balance disorders are common and devastating – it is estimated that one third of US adults over the age of 40 (69 million) have vestibular dysfunction. A major underlying cause of vestibular dysfunction is damage to hair cells in the vestibular organs of the inner ear. Unfortunately in mammals including humans the consequences of this damage are irreversible. The zebrafish has emerged as a model system for studying vestibular function, with its small size and optical clarity advantages for studying hair cells in vivo. Moreover within the zebrafish inner ear, hair cells are able to fully regenerate after damage. Within vestibular organs hair cells are organized into distinct central and peripheral regions with functional and molecular identities highly conserved across species. We propose experiments to study how these spatial identities are initially established within the zebrafish ear. We will determine how hair cells are added during development, and how they undergo phenotypic switching, changing spatial identity during organ growth. We will test how spatial identity regulates regional differences in mitochondrial activity. We will test whether retinoic acid signaling plays a conserved role in zonal patterning. We will test whether transcription factors enriched in zonal expression underlie gene regulatory networks establishing spatial patterning. Together these studies will provide a comprehensive picture for how this core conserved feature of vestibular function is established.