Résumé
The sensory epithelium of the mammalian cochlea (the organ of Corti) represents an excellent developmental system. The organ of Corti contains two main cell types: the sensory hair cells and the supporting cells which are organized in a defined mosaic pattern. Previous results have demonstrated the participation of Notch signaling in the regulation of the pattern of hair cell differentiation within this sensory mosaic. It has also been shown that the basic helix-loop-helix (bHLH) transcription factor Math1 is a positive regulator of hair cell differentiation. We demonstrated that Hes1 and Hes5, two members of the inhibitory bHLH transcription factors, act as negative regulators of hair cell differentiation. Loss-of-function studies implicating the neurogenic genes Notch1, Jag2, Hes1 and Hes5 generated a significant increase in the number of hair cells. However, their functional interplay within the organ of Corti has not been determined. To clarify the mechanisms that regulate hair cell differentiation, we examined the expression of Notch/Notch ligand system and Math1 in the developing organ of Corti of Hes1- and Hes5-deficient mice. Our study suggests complex specific relationships between Notch signaling, Math1 and Hes1/Hes5 in the control of hair cell differentiation in the developing organ of Corti.