EBF1 regulates sensory establishment in the cochlea by positioning the medial boundary of the prosensory domain and restricting proliferation of the sensory progenitor population

Abstract

In our previous study, we reported that Ebf1 excision throughout the inner ear epithelium and before the onset of cochlear development leads to dramatic sensory expansion in the cochlea by neonatal stages. Ebf1 conditional knockout cochleae possess over twice as many sensory cells as littermate controls and develop ectopic sensory patches in their Kollikers organs. To better understand the mechanism behind EBF1s role in restricting sensory establishment, we performed multiome sequencing in our current study. EBF1 is a transcription factor best known for its importance in B cell lineage specification, during which it acts as both an activator and a repressor. Our results indicate that EBF1 prevents the Kollikers organ cells from being recruited to the prosensory domain by promoting expression of Prdm16 and repressing expression of Jag1 and Sox2. We also found that EBF1 may promote cell cycle exit by repressing Ccnjl expression. In summary, medial expansion of the prosensory domain, together with delayed cell cycle exit in the developing cochlear epithelium, underlies the robust increase in sensory cells seen in Ebf1 conditional knockouts. SUMMARY STATEMENTMultiome sequencing reveals EBF1 regulates prosensory domain establishment by: (1) positioning the medial boundary of the prosensory domain and (2) restricting the proliferative capacity of the sensory progenitor pool.