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Publication : The miR-216a-Dot1l Regulatory Axis Is Necessary and Sufficient for Müller Glia Reprogramming during Retina Regeneration.

First Author  Kara N Year  2019
Journal  Cell Rep Volume  28
Issue  8 Pages  2037-2047.e4
PubMed ID  31433981 Mgi Jnum  J:288447
Mgi Id  MGI:6432251 Doi  10.1016/j.celrep.2019.07.061
Citation  Kara N, et al. (2019) The miR-216a-Dot1l Regulatory Axis Is Necessary and Sufficient for Muller Glia Reprogramming during Retina Regeneration. Cell Rep 28(8):2037-2047.e4
abstractText  Unlike the adult mammalian retina, Muller glia (MG) in the adult zebrafish retina are able to dedifferentiate into a "stem cell"-like state and give rise to multipotent progenitor cells upon retinal damage. We show that miR-216a is downregulated in MG after constant intense light lesioning and that miR-216a suppression is necessary and sufficient for MG dedifferentiation and proliferation during retina regeneration. miR-216a targets the H3K79 methyltransferase Dot1l, which is upregulated in proliferating MG after retinal damage. Loss-of-function experiments show that Dot1l is necessary for MG reprogramming and mediates MG proliferation downstream of miR-216a. We further demonstrate that miR-216a and Dot1l regulate MG-mediated retina regeneration through canonical Wnt signaling. This article reports a regulatory mechanism upstream of Wnt signaling during retina regeneration and provides potential targets for enhancing regeneration in the adult mammalian retina.
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