EYA1 and SIX1 drive the neuronal developmental program in cooperation with the SWI/SNF chromatin-remodeling complex and SOX2 in the mammalian inner ear

摘要: Inner ear neurogenesis depends upon the function of proneural basic helix-loop-helix (bHLH) transcription factors NEUROG1 and NEUROD1. However, transcriptional regulation these is unknown. Here, using loss- gain-of-function models, we show that EYA1 SIX1 are crucial otic neuronal determination upstream Overexpression both Eya1 Six1 sufficient to convert non-neuronal epithelial cells within otocyst cochlea as well 3T3 fibroblast into neurons. Strikingly, all ectopic neurons express not only Neurog1 Neurod1 but also mature markers such neurofilament, indicating of, in same pathway as, induce fate regulate their differentiation. We demonstrate interact directly with SWI/SNF chromatin-remodeling subunits BRG1 BAF170 drive cooperatively cochlear nonsensory cells, SOX2 cooperates mediate Importantly, ATPase activity required for EYA1- SIX1-induced normal otocyst. These findings indicate key initiating developmental program, probably by recruiting interacting complex specifically transcription.