PUBLICATION

Tgfb3 collaborates with PP2A and Notch signaling pathways to inhibit retina regeneration

Authors
Lee, M., Wan, J., Goldman, D.
ID
ZDB-PUB-200513-9
Date
2020
Source
eLIFE   9: (Journal)
Registered Authors
Goldman, Dan
Keywords
regenerative medicine, stem cells, zebrafish
Datasets
GEO:GSE145330
MeSH Terms
  • Female
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Transforming Growth Factor beta3/genetics
  • Transforming Growth Factor beta3/metabolism*
  • Smad3 Protein/genetics
  • Smad3 Protein/metabolism
  • Receptors, Notch/metabolism
  • Animals
  • Nerve Regeneration*
  • Male
  • Protein Phosphatase 2/antagonists & inhibitors
  • Protein Phosphatase 2/genetics
  • Protein Phosphatase 2/metabolism*
  • Receptor, Transforming Growth Factor-beta Type I/antagonists & inhibitors
  • Receptor, Transforming Growth Factor-beta Type I/genetics
  • Receptor, Transforming Growth Factor-beta Type I/metabolism
  • Cellular Reprogramming
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Signal Transduction
  • Gene Expression Regulation
  • Neuroglia/cytology
  • Neuroglia/physiology*
  • Retina/cytology
  • Retina/physiology*
  • Cell Proliferation
(all 27)
PubMed
32396062 Full text @ Elife
Abstract
Neuronal degeneration in the zebrafish retina stimulates Müller glia (MG) to proliferate and generate multipotent progenitors for retinal repair. Controlling this proliferation is critical to successful regeneration. Previous studies reported that retinal injury stimulates pSmad3 signaling in injury-responsive MG. Contrary to these findings, we report pSmad3 expression is restricted to quiescent MG and suppressed in injury-responsive MG. Our data indicates that Tgfb3 is the ligand responsible for regulating pSmad3 expression. Remarkably, although overexpression of either Tgfb1b or Tgfb3 can stimulate pSmad3 expression in the injured retina, only Tgfb3 inhibits injury-dependent MG proliferation; suggesting the involvement of a non-canonical Tgfb signaling pathway. Furthermore, inhibition of Alk5, PP2A or Notch signaling rescues MG proliferation in Tgfb3 overexpressing zebrafish. Finally, we report that this Tgfb3 signaling pathway is active in zebrafish MG, but not those in mice, which may contribute to the different regenerative capabilities of MG from fish and mammals.
Genes / Markers
Figures
Figure Gallery (11 images) / 2
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
fb6TgTransgenic Insertion
    jh11TgTransgenic Insertion
      mi4TgTransgenic Insertion
        mi49
          		Indel
          mi50TgTransgenic Insertion
            mi51TgTransgenic Insertion
              nt11TgTransgenic Insertion
                nt19TgTransgenic Insertion
                  1 - 8 of 8
                  Show
                  Human Disease / Model
                  No data available
                  Sequence Targeting Reagents
                  Target Reagent Reagent Type
                  tgfb1bMO2-tgfb1bMRPHLNO
                  tgfb3CRISPR1-tgfb3CRISPR
                  tgfb3MO4-tgfb3MRPHLNO
                  1 - 3 of 3
                  Show
                  Fish
                  Fish
                  fb6Tg
                  jh11Tg
                  jh11Tg; mi51Tg
                  mi4Tg
                  mi50Tg
                  mi51Tg
                  nt11Tg
                  WT
                  1 - 8 of 8
                  Show
                  Antibodies
                  Orthology
                  No data available
                  Engineered Foreign Genes
                  Marker Marker Type Name
                  CeruleanEFGCerulean
                  EGFPEFGEGFP
                  GFPEFGGFP
                  mCherryEFGmCherry
                  1 - 4 of 4
                  Show
                  Mapping
                  No data available
                  Your Input Welcome
                  We welcome your input and comments. Please use this form to recommend updates to the information in ZFIN. We appreciate as much detail as possible and references as appropriate. We will review your comments promptly.
                  Citation
                  Lee, M., Wan, J., Goldman, D. (2020) Tgfb3 collaborates with PP2A and Notch signaling pathways to inhibit retina regeneration. eLIFE. 9:.