Chromatin remodelers and lineage-specific factors interact to target enhancers to establish proneurosensory fate within otic ectoderm

Abstract

Significance The mammalian inner ear uses sensory hair cells and neurons for both auditory and vestibular function. Precursor cells for hair cells and neurons are derived from Sox2 + proneurosensory progenitors specified in the otic ectoderm. Here, we demonstrate that the inner ear neurosensory-specific transcription factor Six1 and its coactivator Eya1 collaborate with chromatin remodelers to promote the initial specification of a proneurosensory-restricted progenitor cell from an ectodermal cell within the otic ectoderm by inducing Sox2 activation. This process is mediated through three distal 3′ Sox2 enhancers whose otic-restricted activity depends on Six1. Our findings have broad implications for understanding the architecture of genetic regulatory circuits that induce the initial events of otic neurosensory lineage establishment and maintenance.