ZFIN ID: ZDB-PUB-121004-18
Insm1a-mediated gene repression is essential for the formation and differentiation of Müller glia-derived progenitors in the injured retina
Ramachandran, R., Zhao, X.F., and Goldman, D.
Date: 2012
Source: Nature cell biology   14(10): 1013-1023 (Journal)
Registered Authors: Goldman, Dan
Keywords: Gene regulation, Regeneration and repair in the nervous system, Retina, Transcription factors
Microarrays: GEO:GSE36191
MeSH Terms:
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors/biosynthesis
  • Cell Differentiation/physiology
  • Cell Proliferation
  • Gene Expression Regulation*
  • Gene Silencing
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins/biosynthesis
  • Nerve Regeneration/genetics
  • Nerve Regeneration/physiology*
  • Neural Stem Cells/physiology*
  • Neuroglia/physiology*
  • Retina/cytology
  • Retina/injuries*
  • Retina/physiology
  • Transcription Factors/genetics
  • Transcription Factors/physiology*
  • Zebrafish/genetics
  • Zebrafish/physiology*
  • Zebrafish Proteins/biosynthesis
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
PubMed: 23000964 Full text @ Nat. Cell Biol.

In zebrafish, retinal injury stimulates Müller glia (MG) reprograming, allowing them to generate multipotent progenitors that replace damaged cells and restore vision. Recent studies suggest that transcriptional repression may underlie these events. To identify transcriptional repressors, we compared the transcriptomes of MG and MG-derived progenitors and identified insm1a, a repressor exhibiting a biphasic pattern of expression that is essential for retina regeneration. Insm1a was found to suppress ascl1a and its own expression, and link injury-dependent ascl1a induction with the suppression of the Wnt inhibitor dickkopf (dkk), which is necessary for MG dedifferentiation. We also found that Insm1a was responsible for sculpting the zone of injury-responsive MG by suppressing hb-egfa expression. Finally, we provide evidence that Insm1a stimulates progenitor cell-cycle exit by suppressing a genetic program driving progenitor proliferation. Our studies identify Insm1a as a key regulator of retina regeneration and provide a mechanistic understanding of how it contributes to multiple phases of this process.