Downstream targets of GATA3 in the vestibular sensory organs of the inner ear

Abstract

Haploinsufficiency for the transcription factor GATA3 leads to hearing loss in humans. It is expressed throughout the auditory sensory epithelium (SE). In the vestibular organs, GATA3 is limited to the striola reversal zone of the utricle. Stereocilia orientation shifts 180 degrees at this region, which contains morphologically distinct type-I hair cells. The striola is conserved in all amniotes, its function is unknown, and GATA3 is the only known marker of the reversal zone. To identify downstream targets of GATA3 that might point to striolar function, we measured gene expression differences between striolar and extra-striolar SE. These were compared with profiles after GATA3 RNAi and GATA3 over-expression. We identified four genes (BMP2, FKHL18, LMO4, and MBNL2) that consistently varied with GATA3. Two of these (LMO4 and MBNL2) were shown to be direct targets of GATA3 by ChIP. Our results suggest that GATA3 impacts WNT signaling in this region of the sensory macula.