Ascl1a regulates Müller glia dedifferentiation and retinal regeneration through a Lin-28-dependent, let-7 microRNA signalling pathway.
Ascl1a regulates Müller glia dedifferentiation and retinal regeneration through a Lin-28-dependent, let-7 microRNA signalling pathway.
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DOI：
10.1038/ncb2115
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发表时间：
2010-11
影响因子：
21.3
通讯作者：
Goldman, Daniel
中科院分区：
文献类型：
--
作者：
Ramachandran, Rajesh;Fausett, Blake V.;Goldman, Daniel
Unlike mammals, teleost fish mount a robust regenerative response to retinal injury that culminates in restoration of visual function. This regenerative response relies on Müller glia (MG) dedifferentiation into a cycling population of progenitor cells. However, the mechanism underlying this dedifferentiation is unknown. Here we report that genes encoding pluripotency factors are induced following retinal injury. Interestingly, the proneural transcription factor Ascl1a and the pluripotency factor Lin-28 are induced in MG within 6 hrs following retinal injury and are necessary for MG dedifferentiation. We demonstrate that Ascl1a is necessary for lin-28 expression and that Lin-28 suppresses let-7 miRNA expression. Furthermore we show that let-7 represses expression of regeneration-associated genes like, ascl1a, hspd1, lin-28, oct4, pax6b and c-myc. Interestingly, hspd1, oct4 and c-myca exhibit basal expression in the uninjured retina and let-7 may inhibit this expression to prevent premature MG dedifferentiation. The opposing actions of Lin-28 and let-7 miRNAs on MG differentiation/dedifferentiation are similar to that of embryonic stem cells and suggest novel targets for stimulating MG dedifferentiation and retina regeneration in mammals.
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影响因子：
14.9
作者：
Chung KH;Hart CC;Al-Bassam S;Avery A;Taylor J;Patel PD;Vojtek AB;Turner DL
通讯作者：
Turner DL
影响因子：
5.3
作者：
Fausett, Blake V.;Gumerson, Jessica D.;Goldman, Daniel
通讯作者：
Goldman, Daniel
影响因子：
5.3
作者：
Bernardos, Rebecca L.;Barthel, Linda K.;Raymond, Pamela A.
通讯作者：
Raymond, Pamela A.
DOI：
10.1073/pnas.0807453105
发表时间：
2008-12-09
影响因子：
11.1
作者：
Karl, Mike O.;Hayes, Susan;Reh, Thomas A.
通讯作者：
Reh, Thomas A.
影响因子：
64.5
作者：
Heo, Inha;Joo, Chirlmin;Kim, V. Narry
通讯作者：
Kim, V. Narry