PUBLICATION
Notch signaling via Hey1 and Id2b regulates Müller glia's regenerative response to retinal injury
- Authors
- Sahu, A., Devi, S., Jui, J., Goldman, D.
- ID
- ZDB-PUB-210821-9
- Date
- 2021
- Source
- Glia 69(12): 2882-2898 (Journal)
- Registered Authors
- Goldman, Dan
- Keywords
- Ascl1, dll4, notch3, reprogramming, stem cell, zebrafish
- Datasets
- GEO:GSE160019, GEO:GSE160051, GEO:GSE160044, GEO:GSE160047, GEO:GSE160179
- MeSH Terms
-
- Animals
- Basic Helix-Loop-Helix Transcription Factors*
- Cell Proliferation/physiology
- Neuroglia*/metabolism
- Receptors, Notch*/metabolism
- Retina/metabolism
- Signal Transduction
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins*/metabolism
- PubMed
- 34415582 Full text @ Glia
Citation
Sahu, A., Devi, S., Jui, J., Goldman, D. (2021) Notch signaling via Hey1 and Id2b regulates Müller glia's regenerative response to retinal injury. Glia. 69(12):2882-2898.
Abstract
Zebrafish Müller glia (MG) respond to retinal injury by suppressing Notch signaling and producing progenitors for retinal repair. A certain threshold of injury-derived signal must be exceeded in order to engage MG in a regenerative response (MG's injury-response threshold). Pan-retinal Notch inhibition expands the zone of injury-responsive MG at the site of focal injury, suggesting that Notch signaling regulates MG's injury-response threshold. We found that Notch signaling enhanced chromatin accessibility and gene expression at a subset of regeneration-associated genes in the uninjured retina. Two Notch effector genes, hey1 and id2b, were identified that reflect bifurcation of the Notch signaling pathway, and differentially regulate MG's injury-response threshold and proliferation of MG-derived progenitors. Furthermore, Notch signaling component gene repression in the injured retina suggests a role for Dll4, Dlb, and Notch3 in regulating Notch signaling in MG and epistasis experiments confirm that the Dll4/Dlb-Notch3-Hey1/Id2b signaling pathway regulates MG's injury-response threshold and proliferation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping