Role of SoxE genes in the development of the auditory portion of the inner ear

The transcription factors of the soxE family, including sox8, sox9 and sox10 play important roles in diverse developmental processes. However little is known about their function during inner ear development. In the developing inner ear we detected sox9 and sox10 in the sensory epithelia since the formation of the otic placode. As the organ of Corti begins to differentiate, sox9 and sox10 expression are progressively restricted to supporting cells. This expression profile prompted us to evaluate the role of SoxE genes in cochlear cell terminal differentiation. Analysis of Sox10 knockout mice showed that it is dispensable for prosensory domain formation but that it is required for its maintenance. Indeed, we observed a significant shortening of the cochlear duct. However, Sox10 does not seem to play a role in cochlear cell fate since cell patterning is not affected in knockout mice. In parallel, we analysed the role of Sox9 in cell specification using both gain- and loss-of function approaches. We demonstrate that Sox9 strongly inhibits hair cell fate even when it is forced by ectopic expression of Atoh1, a potent inducer of hair cell differentiation. Accordingly, Sox9 expression needs to be downregulated in cells that are committed to become hair cells as it was observed in the developing inner ear. To confirm the role of Sox9 in vivo, we also analysed inner ear cell patterning in Sox9a-/-, Sox9b-/- and double knockout zebrafishes at different developmental stages. In parallel, we are investigating the molecular mechanisms underlying Sox9 inhibitory effect on hair cell fate in UB/OC1 cell line and more specifically its relationship with other important factors for cell specification in the organ of Corti such as Sox2, Notch pathway or Atoh1. Taken together, our work is shedding a new light on the role of soxE genes during inner ear development, specification and maintenance of differentiated cells within the cochlea