A GATA3 3= distal otic vesicle enhancer directs inner ear-specific GATA3 expression

Takashi Moriguchi, Tomofumi Hoshino, Arvind Rao, Lei Yu, Jun Takai, Satoshi Uemura, Kazue Ise, Yasuhiro Nakamura, Kim Chew Lim, Ritsuko Shimizu, Masayuki Yamamoto, James Douglas Engel

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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 cis-regulatory element lying 571 kb 3= to the Gata3 gene directs inner ear-specific Gata3 expression, which we refer to as the Gata3 otic vesicle enhancer (OVE). In transgenic murine embryos, a 1.5-kb OVE-directed lacZ reporter (TgOVE-LacZ) exhibited robust lacZ 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 (TgcoreOVE-Cre). TgcoreOVE-Cre successfully marked the OV-derived inner ear tissues, including cochlea, semicircular canal and spiral ganglion, when crossed with ROSA26 lacZ reporter mice. Furthermore, Gata3 conditionally mutant mice, when crossed with the TgcoreOVE-Cre, showed hypoplasia throughout the inner ear tissues. These results demonstrate that OVE has a sufficient regulatory activity to direct Gata3 expression specifically in the otic vesicle and semicircular canal and that Gata3 expression driven by the OVE is crucial for normal inner ear development.

Original languageEnglish
Article numbere0030218
JournalMolecular and cellular biology
Volume38
Issue number21
DOIs
Publication statusPublished - 2018 Nov 1

Keywords

  • Gata3
  • Inner ear
  • Otic vesicle
  • Semicircular canal
  • Yeast artificial chromosome (YAC)

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'A GATA3 3= distal otic vesicle enhancer directs inner ear-specific GATA3 expression'. Together they form a unique fingerprint.

  • Cite this

    Moriguchi, T., Hoshino, T., Rao, A., Yu, L., Takai, J., Uemura, S., Ise, K., Nakamura, Y., Lim, K. C., Shimizu, R., Yamamoto, M., & Engel, J. D. (2018). A GATA3 3= distal otic vesicle enhancer directs inner ear-specific GATA3 expression. Molecular and cellular biology, 38(21), [e0030218]. https://doi.org/10.1128/MCB.00302-18