Journal Article

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

Fausett, Blake V, Goldman, Daniel, Ramachandran, Rajesh

2010

Overview

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 Mueller 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 Mueller glia within 6 h following retinal injury and are necessary for Mueller 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-myc sub(a) exhibit basal expression in the uninjured retina and let-7 may inhibit this expression to prevent premature Mueller glia dedifferentiation. The opposing actions of Lin-28 and let-7 miRNAs on Mueller glia differentiation and dedifferentiation are similar to that of embryonic stem cells and suggest novel targets for stimulating Mueller glia dedifferentiation and retinal regeneration in mammals.

• Subject: Teleostei