Gata3 is Required in Late Proneurosensory Development for Proper Sensory Cell Formation and Organization

Abstract

Abstract It has been previously shown that 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 to which Gata3 is required for the formation of the cochlear neurosensory epithelia remains unclear. To investigate the role of Gata3 on cochlear neurosensory development in the late prosensory stages, we used the Sox2-creERT2 mouse line to target and conditionally delete Gata3 at E11.5 before the cells have fully committed to a neurosensory fate. While the inner ears of Sox2-creERT2: Gata3 f/f mice appear morphologically normal, the sensory cells in the organ of Corti are partially lost and disorganized in a basal to apical gradient with the apex demonstrating the more severe phenotype. Additionally, spiral ganglion neurons display aberrant peripheral projections, such as increased distances between radial bundles and disorganization upon reaching the organ of Corti. Furthermore, heterozygous Sox2-creERT2: Gata3 f/+ mice show a reduced phenotype in comparison to the homozygous mutant, supporting the concept that Gata3 is not only required for proper formation at the later proneurosensory stage, but also that a specific level of Gata3 is required. Therefore, our studies confirm that Gata3 plays a time-sensitive and dose-dependent role in the development of sensory cells in the late proneurosensory stages.