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Ascl1a regulates Müller glia dedifferentiation and retinal regeneration through a Lin-28-dependent, let-7 microRNA signalling pathway

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Ramachandran, Rajesh, Fausett, Blake V., Goldman, Daniel·2010·Nature Cell Biology
DOI 10.1038/ncb2115
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Abstract

Unlike mammals, teleost fish mount a robust regenerative response to retinal injury that culminates in restoration of visual function. This regenerative response relies on dedifferentiation of Müller glia 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 Müller glia within 6 h following retinal injury and are necessary for Müller glia dedifferentiation. We demonstrate that Ascl1a is necessary for lin-28 expression and that Lin-28 suppresses let-7 microRNA (miRNA) expression. Furthermore, we demonstrate that let-7 represses expression of regeneration-associated genes such as, ascl1a, hspd1, lin-28, oct4, pax6b and c-myc. hspd1, oct4 and c-myca exhibit basal expression in the uninjured retina and let-7 may inhibit this expression to prevent premature Müller glia dedifferentiation. The opposing actions of Lin-28 and let-7 miRNAs on Müller glia differentiation and dedifferentiation are similar to that of embryonic stem cells and suggest novel targets for stimulating Müller glia dedifferentiation and retinal regeneration in mammals.

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Research works printed but not linked: 35

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Metadata

Authors
Ramachandran, R., Fausett, B. V., & Goldman, D.
Venue
Nature Cell Biology
Publisher
Springer Science and Business Media LLC
Published
2010-10-10
Volume
12
Issue
11
Pages
1101-1107
ISSN
  • 1465-7392 (ISSN-L)
  • 1476-4679
DOI
10.1038/ncb2115
OpenAlex
W1979509436
Cited by
366
References
5
FWCI
6.73
Type
journal article
Language
en
Update notices
erratum (2015-03-27)
Open access
green
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CoChat. (2026). Citation check: Ascl1a regulates Müller glia dedifferentiation and retinal regeneration through a Lin-28-dependent, let-7 microRNA signalling pathway. https://app.cochat.ai/papers/10.1038/ncb2115
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Ramachandran, R., Fausett, B. V., & Goldman, D. (2010). Ascl1a regulates Müller glia dedifferentiation and retinal regeneration through a Lin-28-dependent, let-7 microRNA signalling pathway. Nature Cell Biology. https://doi.org/10.1038/ncb2115

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