Fig. 7.

Model of Atoh1 regulation during organ of Corti development. Upregulation of Atoh1 in groups of cells within the embryonic prosensory domain occurs in a basal-to-apical wave. Once the Atoh1 autoregulatory threshold is achieved in selected nascent hair cells, Notch-mediated active repression is triggered in the surrounding prosensory cells to stimulate the silencing of Atoh1 through Hes/Hey binding, leading to the onset of supporting cell differentiation and the patterning of the cellular mosaic of the organ of Corti. At P1, cell fate is maintained by continuing Notch-mediated repression through recruitment of GRG/HDACs. Loss of Notch activity leads to derepression of the Atoh1 promoter and increased Atoh1 expression through hypothetical positive transcriptional activity (TF-X), leading to autoregulation and transdifferentiation of supporting cells (SC) to a hair cell-like state (HC).