Ids regulate Math1 and hair cell differentiation during the development of the organ of Corti.

摘要

The sensory epithelium of the mammalian cochlea (organ of Corti) is a highly ordered regular pattern made up of sensory hair cells and nonsensory supporting cells. The molecular mechanisms underlying the development of this epithelium are just beginning to be understood. We know very little about the development of the supporting cells but there has been some interesting data giving us insight into the development of sensory hair cells. The basic Helix-Loop-Helix (bHLH) transcription factor Math1 (also called Atoh1) is both necessary and sufficient for hair cell development in the mammalian cochlea. Previous studies have demonstrated that a dynamic pattern of Math1 expression plays a key role in regulating the number and position of mechanosensory hair cells. However the factors that regulate the temporal and spatial expression of Math1 within the cochlea are unknown. The bHLH-related Id proteins are known to negatively regulate many bHLH transcription factors including Math1, in a number of different systems. Therefore, Id proteins are good candidates for playing a role in regulating Math1 in the cochlea.Results from RT-PCR and in situ hybridization indicate that Ids1-3 are expressed within the cochlear duct at relevant developmental stages in patterns that are consistent with a role in regulation of hair cell development. The expression patterns show that where prior to hair cell differentiation, both Id1 and Math1 were expressed in cochlear progenitor cells but once cellular differentiation began, Id1 expression was downregulated in cells that express Math1 and differentiated as hair cells. Finally forced expression of Ids within cochlear progenitor cells leads to a significant inhibition of hair cell development and expression of Math1. These results indicate a novel mechanism in which Ids play a key role in regulating Math1 and hair cell differentiation in the developing cochlea.