PUBLICATION

NeuroD regulates proliferation of photoreceptor progenitors in the retina of the zebrafish

Authors
Ochocinska, M.J., and Hitchcock, P.F.
ID
ZDB-PUB-090106-41
Date
2009
Source
Mechanisms of Development   126(3-4): 128-141 (Journal)
Registered Authors
Hitchcock, Peter
Keywords
none
MeSH Terms
  • Cell Proliferation/drug effects
  • Recombinant Fusion Proteins/metabolism
  • Fertilization/drug effects
  • Mitosis/drug effects
  • Embryonic Development/drug effects
  • Up-Regulation/drug effects
  • Retinal Rod Photoreceptor Cells/cytology
  • Retinal Rod Photoreceptor Cells/drug effects
  • Retinal Rod Photoreceptor Cells/metabolism
  • Photoreceptor Cells, Vertebrate/cytology*
  • Photoreceptor Cells, Vertebrate/drug effects
  • Photoreceptor Cells, Vertebrate/metabolism
  • Oligonucleotides, Antisense/pharmacology
  • Retina/cytology*
  • Retina/drug effects
  • Retina/metabolism
  • Animals, Genetically Modified
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Stem Cells/cytology*
  • Stem Cells/drug effects
  • Stem Cells/metabolism
  • Basic Helix-Loop-Helix Transcription Factors/metabolism*
  • Neuroglia/cytology
  • Neuroglia/drug effects
  • Neuroglia/metabolism
  • Gene Expression Regulation, Developmental/drug effects
  • Animals
  • Cyclins/genetics
  • Cyclins/metabolism
  • Cell Differentiation/drug effects
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/metabolism
  • Nerve Tissue Proteins/metabolism*
(all 36)
PubMed
19121642 Full text @ Mech. Dev.
Abstract
neuroD is a member of the family of proneural genes, which function to regulate the cell cycle, cell fate determination and cellular differentiation. In the retinas of larval and adult teleosts, neuroD is expressed in two populations of post-mitotic cells, a subset of amacrine cells and nascent cone photoreceptors, and proliferating cells in the lineages that give rise exclusively to rod and cone photoreceptors. Based on previous studies of NeuroD function in vitro and the cellular pattern of neuroD expression in the zebrafish retina, we hypothesized that within the mitotic photoreceptor lineages NeuroD selectively regulates aspects of the cell cycle. To test this hypothesis, gain and loss-of-function approaches were employed, relying on the inducible expression of a NeuroD(EGFP) fusion protein and morpholino oligonucleotides to inhibit protein translation, respectively. Conditional expression of neuroD causes cells to withdraw from the cell cycle, upregulate the expression of the cell cycle inhibitors, p27 and p57, and downregulate the cell cycle progression factors, Cyclin B1, Cyclin D1, and Cyclin E2. In the absence of NeuroD, cells specific for the rod and cone photoreceptor lineage fail to exit the cell cycle, and the number of cells expressing Cyclin D1 is increased. When expression is ectopically induced in multipotent progenitors, neuroD promotes the genesis of rod photoreceptors and inhibits the genesis of Müller glia. These data show that in the teleost retina NeuroD plays a fundamental role in photoreceptor genesis by regulating mechanisms that promote rod and cone progenitors to withdraw from the cell cycle. This is the first in vivo demonstration in the retina of cell cycle regulation by NeuroD.
Genes / Markers
Figures
Figure Gallery (12 images) / 2
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
zf202TgTransgenic Insertion
    zf203TgTransgenic Insertion
      zf204TgTransgenic Insertion
        1 - 3 of 3
        Show
        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        neurod1MO1-neurod1MRPHLNO
        1 - 1 of 1
        Show
        Fish
        Fish
        zf202Tg/zf202Tg
        zf203Tg/zf203Tg
        zf204Tg/zf204Tg
        1 - 3 of 3
        Show
        Antibodies
        Orthology
        No data available
        Engineered Foreign Genes
        Marker Marker Type Name
        EGFPEFGEGFP
        1 - 1 of 1
        Show
        Mapping
        No data available
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        Citation
        Ochocinska, M.J., and Hitchcock, P.F. (2009) NeuroD regulates proliferation of photoreceptor progenitors in the retina of the zebrafish. Mechanisms of Development. 126(3-4):128-141.