Ascl1a regulates Müller glia dedifferentiation and retinal regeneration through a Lin-28-dependent, let-7 microRNA signalling pathway
- Ramachandran, R., Fausett, B.V., and Goldman, D.
- Nature cell biology 12(11): 1101-1107 (Journal)
- Registered Authors
- Goldman, Dan
- MeSH Terms
- Basic Helix-Loop-Helix Transcription Factors/metabolism*
- Cell Dedifferentiation*
- RNA-Binding Proteins/genetics
- RNA-Binding Proteins/metabolism*
- Signal Transduction*
- Zebrafish Proteins/metabolism*
- 20935637 Full text @ Nat. Cell Biol.
Ramachandran, R., Fausett, B.V., and Goldman, D. (2010) Ascl1a regulates Müller glia dedifferentiation and retinal regeneration through a Lin-28-dependent, let-7 microRNA signalling pathway. Nature cell biology. 12(11):1101-1107.
Unlike mammals, teleost fish mount a robust regenerative response to retinal injury that culminates in restoration of visual function1, 2. 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 cells3 and suggest novel targets for stimulating Müller glia dedifferentiation and retinal regeneration in mammals.
Errata / NotesThis article is corrected by ZDB-PUB-220906-15.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes