Gene regulatory networks controlling vertebrate retinal regeneration

Thanh Hoang, Jie Wang, Patrick Boyd, Fang Wang, Clayton Santiago, Lizhi Jiang, Sooyeon Yoo, Manuela Lahne, Levi J. Todd, Meng Jia, Cristian Saez, Casey Keuthan, Isabella Palazzo, Natalie Squires, Warren A. Campbell, Fatemeh Rajaii, Trisha Parayil, Vickie Trinh, Dong Won Kim, Guohua WangLeah J. Campbell, John Ash, Andy J. Fischer, David R. Hyde, Jiang Qian, Seth Blackshaw

Research output: Contribution to journalArticlepeer-review

Abstract

Injury induces retinal Müller glia of certain cold-blooded vertebrates, but not those of mammals, to regenerate neurons. To identify gene regulatory networks that reprogram Müller glia into progenitor cells, we profiled changes in gene expression and chromatin accessibility in Müller glia from zebrafish, chick, and mice in response to different stimuli. We identified evolutionarily conserved and speciesspecific gene networks controlling glial quiescence, reactivity, and neurogenesis. In zebrafish and chick, the transition from quiescence to reactivity is essential for retinal regeneration, whereas in mice, a dedicated network suppresses neurogenic competence and restores quiescence. Disruption of nuclear factor I transcription factors, which maintain and restore quiescence, induces Müller glia to proliferate and generate neurons in adult mice after injury. These findings may aid in designing therapies to restore retinal neurons lost to degenerative diseases.

Original languageEnglish (US)
Article numbereabb8598
JournalScience
Volume370
Issue number6519
DOIs
StatePublished - Nov 20 2020

ASJC Scopus subject areas

  • General

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