A 3' Distal Otic Vesicle Enhancer Directs Inner Ear-Specific Expression.

Transcription factor GATA3 plays vital roles in inner ear development, while regulatory mechanisms controlling its inner ear-specific expression are undefined. We demonstrate that a -regulatory element lying 571 kb 3' to the gene directs inner ear-specific expression, which we refer to as the otic vesicle enhancer (OVE). In transgenic murine embryos, a 1.5-kb OVE-directed reporter (Tg) exhibited robust expression specifically in the otic vesicle (OV), an inner ear primordial tissue, and its derivative semicircular canal. To further define the regulatory activity of this OVE, we generated Cre transgenic mice in which Cre expression was directed by a 246-bp core sequence within the OVE element (Tg). Tg successfully marked the OV-derived inner ear tissues, including cochlea, semicircular canal and spiral ganglion, when crossed with ROSA26 reporter mice. Furthermore, conditionally mutant mice, when crossed with the Tg, showed hypoplasia throughout the inner ear tissues. These results demonstrate that OVE has a sufficient regulatory activity to direct expression specifically in the otic vesicle and semicircular canal and that expression driven by the OVE is crucial for normal inner ear development.