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Abstract :
[en] It is widely accepted that cell fate determination in the cochlea is tightly controlled by different factors that remain to be fully defined. Here, we show that Sox9, initially expressed in the entire sensory epithelium of the cochlea, progressively disappears from differentiating hair cells (HCs) and is finally restricted to supporting cells (SCs). The absence of Sox9 leads to supernumerary HCs production, and its overexpression blocks HCs differentiation even if co-expressed with Atoh1, a transcription factor necessary and sufficient to induce HCs. Sox9 reduces Atoh1 transcriptional activity by upregulating Hey1 and HeyL factors and genetic ablation of these genes induce extra HCs along the cochlea. Furthermore, we show that Sox9 is required for Notch-dependent inhibition of HC fate. Taken together, these data show that Sox9 contributes to Notch-dependent cochlear cell patterning by upregulating Hey1 and HeyL proteins in future SCs, thereby preventing Atoh1 from driving HC differentiation.