GSE131165
Genome-wide enhancer profiling identifies novel Shh regulated gene targets in the developing cochlear duct
The development of the mammalian inner ears is a highly dynamic process that is dependent on the interplay of multiple signaling molecules. Previous studies demonstrated the role of Shh in the initiation and outgrowth of the cochlea. However, the gene targets of Shh in the cochlea largely remain unknown. We show in this study, Shh responsive genes that are loss in the cochlea of Smoecko mutant (Smo null) and upregulated in Shh-P1 mutant embryos through comparative RNA-seq profiling. We performed a genome-wide cis-regulatory element (cRE) study (via ATAC-seq and Gli2 ChIP-seq) and identified potential cREs that are targets of the Shh signaling pathway in   the cochlea. Our data unravel novel Shh signaling regulated gene targets that have important functional roles in the development of the cochlea. Overall design: 1) Examination of genome wide gene expression in 2 different inner ear mutants at E11.5, 2) Examination genome wide of open chromatin regions using ATAC-seq in E11.5 inner ear, 3) Examination of genome wide Gli2 binding site in the E10.5 embryonic head