Gata3 is required in late proneurosensory development for proper sensory cell formation and organization

Abstract

AbstractIt has previously been shown that the zinc-finger transcription factor Gata3 has dynamic expression within the inner ear throughout embryonic development and is essential for cochlear neurosensory development. However, the temporal window for which Gata3 is required for proper formation of the cochlear neurosensory epithelia remains unclear. To investigate the role of Gata3 in cochlear neurosensory development in the late prosensory stages, we used the Sox2-creERT2 mouse line to target and conditionally delete Gata3 at E11.5, a timepoint before cells have fully committed to a neurosensory fate. While the inner ears of Sox2-creERT2: Gata3 f/f mice appear normal with no gross structural defects, the sensory cells in the organ of Corti are partially lost and disorganized in an increasing severity from base to apex. Additionally, spiral ganglion neurons display aberrant peripheral projections, including increased distances between radial bundles and disorganization upon reaching the organ of Corti. Furthermore, heterozygous Sox2-creERT2: Gata3 f/+ mice show a reduced aberrant phenotype in comparison to the homozygous mutant, supporting the hypothesis that Gata3 is not only required for proper formation at the later proneurosensory stage, but also that a specific expression level of Gata3 is required. Therefore, this study provides evidence that Gata3 plays a time-sensitive and dose-dependent role in the development of sensory and neuronal cells in late proneurosensory stages.