ZFIN ID: ZDB-PUB-170406-1
Progranulin regulates neurogenesis in the developing vertebrate retina
Walsh, C.E., Hitchcock, P.F.
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.
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.