PUBLICATION

Asymmetric neurogenic commitment of retinal progenitors involves Notch through the endocytic pathway

Authors
Nerli, E., Rocha-Martins, M., Norden, C.
ID
ZDB-PUB-201120-11
Date
2020
Source
eLIFE   9: (Journal)
Registered Authors
Nerli, Elisa, Norden, Caren
Keywords
developmental biology, zebrafish
MeSH Terms
  • Alanine/analogs & derivatives
  • Alanine/pharmacology
  • Animals
  • Animals, Genetically Modified
  • Azepines/pharmacology
  • Cell Proliferation/drug effects
  • Diamines/pharmacology
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental/drug effects
  • Gene Knockdown Techniques
  • Microscopy, Confocal/methods
  • Neural Stem Cells/physiology*
  • Neurogenesis/physiology*
  • Receptors, Notch/antagonists & inhibitors*
  • Receptors, Notch/metabolism
  • Retinal Neurons/physiology*
  • Thiazoles/pharmacology
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
33141024 Full text @ Elife
Abstract
During brain development, progenitor cells need to balance proliferation and differentiation in order to generate different neurons in the correct numbers and proportions. Currently, the patterns of multipotent progenitor divisions that lead to neurogenic entry and the factors that regulate them are not fully understood. We here use the zebrafish retina to address this gap, exploiting its suitability for quantitative live-imaging. We show that early neurogenic progenitors arise from asymmetric divisions. Notch regulates this asymmetry, as when inhibited, symmetric divisions producing two neurogenic progenitors occur. Surprisingly however, Notch does not act through an apicobasal activity gradient as previously suggested, but through asymmetric inheritance of Sara-positive endosomes. Further, the resulting neurogenic progenitors show cell biological features different from multipotent progenitors, raising the possibility that an intermediate progenitor state exists in the retina. Our study thus reveals new insights into the regulation of proliferative and differentiative events during central nervous system development.
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Mutations / Transgenics
Human Disease / Model
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