PUBLICATION

Progranulin regulates neurogenesis in the developing vertebrate retina

Authors
Walsh, C.E., Hitchcock, P.F.
ID
ZDB-PUB-170406-1
Date
2017
Source
Developmental Neurobiology   77(9): 1114-1129 (Journal)
Registered Authors
Hitchcock, Peter
Keywords
CNS Development, Cell Cycle, Progranulin-a, Retinal Development, Zebrafish
MeSH Terms
  • Analysis of Variance
  • Animals
  • Bromodeoxyuridine/metabolism
  • Cell Cycle/drug effects
  • Cell Cycle/physiology
  • Cell Differentiation/drug effects
  • Cell Differentiation/physiology
  • Cell Proliferation/drug effects
  • Cell Proliferation/physiology
  • Cyclin-Dependent Kinase Inhibitor p27/metabolism
  • Cyclin-Dependent Kinase Inhibitor p57/metabolism
  • Cyclins/metabolism
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental/drug effects
  • Gene Expression Regulation, Developmental/genetics*
  • Green Fluorescent Proteins/genetics
  • Green Fluorescent Proteins/metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins/genetics
  • Intercellular Signaling Peptides and Proteins/metabolism*
  • Microglia/drug effects
  • Neurogenesis/drug effects
  • Neurogenesis/genetics
  • Neurogenesis/physiology*
  • Oligonucleotides, Antisense/pharmacology
  • Retina/cytology
  • Retina/embryology*
  • Retina/metabolism*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
28380680 Full text @ Dev. Neurobiol.
Abstract
We evaluated the expression and function of the microglia-specific growth factor, Progranulin-a (Pgrn-a) during developmental neurogenesis in the embryonic retina of zebrafish. At 24 hpf pgrn-a is expressed throughout the forebrain, but by 48 hpf pgrn-a is exclusively expressed by microglia and/or microglial precursors within the brain and retina. Knockdown of Pgrn-a does not alter the onset of neurogenic programs or increase cell death, however, in its absence, neurogenesis is significantly delayed - retinal progenitors fail to exit the cell cycle at the appropriate developmental time and postmitotic cells do not acquire markers of terminal differentiation, and microglial precursors do not colonize the retina. Given the link between Progranulin and cell cycle regulation in peripheral tissues and transformed cells, we analyzed cell cycle kinetics among retinal progenitors following Pgrn-a knockdown. Depleting Pgrn-a results in a significant lengthening of the cell cycle. These data suggest that Pgrn-a plays a dual role during nervous system development by governing the rate at which progenitors progress through the cell cycle and attracting microglial progenitors into the embryonic brain and retina. Collectively, these data show that Pgrn-a governs neurogenesis by regulating cell cycle kinetics and the transition from proliferation to cell cycle exit and differentiation. This article is protected by copyright. All rights reserved.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping