Notch pathway inhibitor DAPT enhances Atoh1 activity to generate new hair cells in situ in rat cochleae

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 ce...

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Main Authors: Wen-wei Luo, Zhao Han, Dong-dong Ren, Xin-wei Wang, Fang-lu Chi, Juan-mei Yang
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2017-01-01
Series:Neural Regeneration Research
Subjects:
Online Access:http://www.nrronline.org/article.asp?issn=1673-5374;year=2017;volume=12;issue=12;spage=2092;epage=2099;aulast=Luo
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author Wen-wei Luo
Zhao Han
Dong-dong Ren
Xin-wei Wang
Fang-lu Chi
Juan-mei Yang
author_facet Wen-wei Luo
Zhao Han
Dong-dong Ren
Xin-wei Wang
Fang-lu Chi
Juan-mei Yang
author_sort Wen-wei Luo
collection DOAJ
description 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.
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spelling doaj.art-7e76124ad9324b6bb15efadd48a5ce742022-12-21T19:38:44ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742017-01-0112122092209910.4103/1673-5374.221169Notch pathway inhibitor DAPT enhances Atoh1 activity to generate new hair cells in situ in rat cochleaeWen-wei LuoZhao HanDong-dong RenXin-wei WangFang-lu ChiJuan-mei YangAtoh1 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.http://www.nrronline.org/article.asp?issn=1673-5374;year=2017;volume=12;issue=12;spage=2092;epage=2099;aulast=Luonerve regeneration; Atoh1; DAPT; transdifferentiation; gamma secretase inhibitor; cochlea; sensory epithelium; fetal bovine serum; hair cell; supporting cell; hair cell regeneration; neural regeneration
spellingShingle Wen-wei Luo
Zhao Han
Dong-dong Ren
Xin-wei Wang
Fang-lu Chi
Juan-mei Yang
Notch pathway inhibitor DAPT enhances Atoh1 activity to generate new hair cells in situ in rat cochleae
Neural Regeneration Research
nerve regeneration; Atoh1; DAPT; transdifferentiation; gamma secretase inhibitor; cochlea; sensory epithelium; fetal bovine serum; hair cell; supporting cell; hair cell regeneration; neural regeneration
title Notch pathway inhibitor DAPT enhances Atoh1 activity to generate new hair cells in situ in rat cochleae
title_full Notch pathway inhibitor DAPT enhances Atoh1 activity to generate new hair cells in situ in rat cochleae
title_fullStr Notch pathway inhibitor DAPT enhances Atoh1 activity to generate new hair cells in situ in rat cochleae
title_full_unstemmed Notch pathway inhibitor DAPT enhances Atoh1 activity to generate new hair cells in situ in rat cochleae
title_short Notch pathway inhibitor DAPT enhances Atoh1 activity to generate new hair cells in situ in rat cochleae
title_sort notch pathway inhibitor dapt enhances atoh1 activity to generate new hair cells in situ in rat cochleae
topic nerve regeneration; Atoh1; DAPT; transdifferentiation; gamma secretase inhibitor; cochlea; sensory epithelium; fetal bovine serum; hair cell; supporting cell; hair cell regeneration; neural regeneration
url http://www.nrronline.org/article.asp?issn=1673-5374;year=2017;volume=12;issue=12;spage=2092;epage=2099;aulast=Luo
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