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Role of SoxE genes in the development of the auditory portion of the inner ear
Delacroix, Laurence
2013The Belgian Society for Neurosciences Annual Meeting
 

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Keywords :
hearing; development; inner ear
Abstract :
[en] The transcription factors of the SoxE family, including Sox8, Sox9 and Sox10 play important roles in diverse developmental processes and particularly in the development of the auditory portion of the inner ear, the cochlea. Among these regulatory genes, Sox9 has been shown to be important in otic vesicle formation during early embryonic development. Indeed, Sox9 expression is detected as soon as embryonic day E9, in the forming otic placode. As the organ of Corti begins to differentiate, Sox9 is progressively restricted to supporting cells and its expression is absent from hair cells, responsible for sound transduction. This expression profile prompted us to evaluate the role of this gene in cochlear cell terminal differentiation. We therefore analysed the role of Sox9 in cell specification using both gain- and loss-of function approaches. We demonstrated, by ex vivo electroporation of mouse embryonic cochlea that Sox9 strongly inhibits hair cell fate even when it is forced by ectopic expression of Atoh1, a potent inducer of hair cell differentiation. On the contrary, suppression of Sox9 in sensory progenitors did not affect cell fate. We also showed that Sox9 is upregulated by Notch activation in mouse embryonic cochlea and partially contributes to Notch inhibition of hair cell fate. Loss of Notch signaling in cells that are committed to become hair cells could thus be responsible for Sox9 suppression in these cells. In parallel, we investigated the molecular mechanisms underlying Sox9 inhibitory effect on hair cell fate in UB/OC1 cell line (derived from mouse embryonic otocyst) and more specifically its relationship with other important factors for cell specification. We observed an inhibition of Atoh1 transcriptional activity upon Sox9 overexpression, concomitant with an increase in the expression levels of Hey1 and HeyL factors. These proteins are well-known effectors of the Notch cascade and act by inhibiting Atoh1 activity. Taken together, our data suggest that Sox9 potentiates Notch pathway by upregulating its effectors Hey1 and HeyL and that Sox9 misexpression in differentiating hair cells inhibits the activity of the major hair cell fate inducer Atoh1, thereby preventing sensory cell terminal differentiation.
Disciplines :
Anatomy (cytology, histology, embryology...) & physiology
Author, co-author :
Delacroix, Laurence ;  Université de Liège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Language :
English
Title :
Role of SoxE genes in the development of the auditory portion of the inner ear
Publication date :
2013
Event name :
The Belgian Society for Neurosciences Annual Meeting
Event place :
Ghent, Belgium
Event date :
May 31st
Audience :
International
Available on ORBi :
since 05 July 2016

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