Atoh1 overexpression in cochlear epithelium induces new hair cell formation. Use of adenovirus-mediated Atoh1 overexpression has mainly focused on the rat lesser epithelial ridge and induces ectopic hair cell regenera...Atoh1 overexpression in cochlear epithelium induces new hair cell formation. Use of adenovirus-mediated Atoh1 overexpression has mainly focused on the rat lesser epithelial ridge and induces ectopic hair cell regeneration. The sensory region of rat cochlea is difficult to transfect, thus new hair cells are rarely produced in situ in rat cochlear explants. After culturing rat cochleae in medium containing 10% fetal bovine serum, adenovirus successfully infected the sensory region as the width of the supporting cell area was significantly increased. Adenovirus encoding Atoh1 infected the sensory region and induced hair cell formation in situ. Combined application of the Notch inhibitor DAPT and Atoh1 increased the Atoh1 expression level and decreased hes1 and hes5 levels, further promoting hair cell generation. Our results demonstrate that DAPT enhances Atoh1 activity to promote hair cell regeneration in rat cochlear sensory epithelium in vitro.展开更多
More than 80%of all cases of deafness are related to the death or degeneration of cochlear hair cells and the associated spiral ganglion neurons,and a lack of regeneration of these cells leads to permanent hearing los...More than 80%of all cases of deafness are related to the death or degeneration of cochlear hair cells and the associated spiral ganglion neurons,and a lack of regeneration of these cells leads to permanent hearing loss.Therefore,the regeneration of lost hair cells is an important goal for the treatment of deafness.Atoh1 is a basic helix-loop-helix(bHLH)transcription factor that is critical in both the development and regeneration of cochlear hair cells.Atoh1 is transcriptionally regulated by several signaling pathways,including Notch and Wnt signalings.At the post-translational level,it is regulated through the ubiquitin-proteasome pathway.In vitro and in vivo studies have revealed that manipulation of these signaling pathways not only controls development,but also leads to the regeneration of cochlear hair cells after damage.Recent progress toward understanding the signaling networks involved in hair cell development and regeneration has led to the development of new strategies to replace lost hair cells.This review focuses on our current understanding of the signaling pathways that regulate Atoh1 in the cochlea.展开更多
基金supported by the National Natural Science Foundation of China,No.81420108010,81271084,81200740,81371093
文摘Atoh1 overexpression in cochlear epithelium induces new hair cell formation. Use of adenovirus-mediated Atoh1 overexpression has mainly focused on the rat lesser epithelial ridge and induces ectopic hair cell regeneration. The sensory region of rat cochlea is difficult to transfect, thus new hair cells are rarely produced in situ in rat cochlear explants. After culturing rat cochleae in medium containing 10% fetal bovine serum, adenovirus successfully infected the sensory region as the width of the supporting cell area was significantly increased. Adenovirus encoding Atoh1 infected the sensory region and induced hair cell formation in situ. Combined application of the Notch inhibitor DAPT and Atoh1 increased the Atoh1 expression level and decreased hes1 and hes5 levels, further promoting hair cell generation. Our results demonstrate that DAPT enhances Atoh1 activity to promote hair cell regeneration in rat cochlear sensory epithelium in vitro.
文摘More than 80%of all cases of deafness are related to the death or degeneration of cochlear hair cells and the associated spiral ganglion neurons,and a lack of regeneration of these cells leads to permanent hearing loss.Therefore,the regeneration of lost hair cells is an important goal for the treatment of deafness.Atoh1 is a basic helix-loop-helix(bHLH)transcription factor that is critical in both the development and regeneration of cochlear hair cells.Atoh1 is transcriptionally regulated by several signaling pathways,including Notch and Wnt signalings.At the post-translational level,it is regulated through the ubiquitin-proteasome pathway.In vitro and in vivo studies have revealed that manipulation of these signaling pathways not only controls development,but also leads to the regeneration of cochlear hair cells after damage.Recent progress toward understanding the signaling networks involved in hair cell development and regeneration has led to the development of new strategies to replace lost hair cells.This review focuses on our current understanding of the signaling pathways that regulate Atoh1 in the cochlea.
