PUBLICATION

Depletion of Polypyrimidine tract binding protein 1 (ptbp1) activates Müller glia-derived proliferation during zebrafish retina regeneration via modulation of the senescence secretome

Authors
Konar, G.J., Lingan, A.L., Vallone, K.T., Nguyen, T.D., Flickinger, Z.R., Patton, J.G.
ID
ZDB-PUB-250513-1
Date
2025
Source
Experimental Eye Research : 110420110420 (Journal)
Registered Authors
Patton, James G.
Keywords
SASP, regeneration, retina, senescence
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Cell Proliferation/physiology
  • Cellular Senescence/physiology
  • Disease Models, Animal
  • Ependymoglial Cells*/cytology
  • Ependymoglial Cells*/metabolism
  • Polypyrimidine Tract-Binding Protein*/genetics
  • Polypyrimidine Tract-Binding Protein*/physiology
  • Regeneration*/physiology
  • Retina*/physiology
  • Zebrafish
  • Zebrafish Proteins*/genetics
PubMed
40355064 Full text @ Exp. Eye. Res.
Abstract
Polypyrimidine Tract Binding protein 1 (PTB) is an alternative splicing factor linked to neuronal induction and maturation. Previously, knockdown experiments supported a model in which PTB can function as a potent reprogramming factor, able to elicit direct glia-to-neuron conversion in vivo, in both the brain and retina. However, later lineage tracing and genetic knockouts of PTB did not support direct neuronal reprogramming. Nevertheless, consistent with the PTB depletion experiments, we show that antisense knockdown of PTB (ptbp1a) in the zebrafish retina can activate Müller glia-derived proliferation and that depletion of PTB can further enhance proliferation when combined with acute NMDA damage. The effects of PTB are consistent with a role in controlling key senescence and pro-inflammatory genes that are part of the senescence secretome that initiates retina regeneration.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping