摘要：Haplo-insufficiency of the
GATA3 gene causes hypoparathyroidism, sensorineural hearing loss, and renal disease (HDR) syndrome. Previous studies have shown that
Gata3 is required for the development of the prosensory domain and spiral ganglion neurons (SGNs) of the mouse cochlea during embryogenesis. However, its role in supporting cells (SCs) after cell fate specification is largely unknown. In this study, we used tamoxifen-inducible
Sox2
CreERT2
mice to delete
Gata3 in SCs of the neonatal mouse cochlea and showed that loss of
Gata3 resulted in the proliferation of SCs, including the inner pillar cells (IPCs), inner border cells (IBCs), and lateral greater epithelium ridge (GER). In addition, loss of
Gata3 resulted in the down-regulation of p27
kip1, a cell cycle inhibitor, in the SCs of
Gata3-CKO neonatal cochleae. Chromatin immunoprecipitation analysis revealed that GATA3 directly binds to
p27
kip1
promoter and could maintain the quiescent state of cochlear SCs by regulating
p27
kip1
expression. Furthermore, RNA-seq analysis revealed that loss of
Gata3 function resulted in the change in the expression of genes essential for the development and function of cochlear SCs, including
Tectb,
Cyp26b1,
Slitrk6,
Ano1, and
Aqp4.
