PUBLICATION

Photoreceptor Progenitors Depend Upon Coordination of gdf6a, thrβ, and tbx2b to Generate Precise Populations of Cone Photoreceptor Subtypes

Authors
DuVal, M.G., Allison, W.T.
ID
ZDB-PUB-181230-11
Date
2018
Source
Investigative ophthalmology & visual science   59: 6089-6101 (Journal)
Registered Authors
Allison, Ted, Duval, Michèle
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation/physiology*
  • Embryo, Nonmammalian
  • Gene Expression Regulation/physiology
  • Gene Silencing
  • Genotyping Techniques
  • Growth Differentiation Factor 6/physiology*
  • Immunohistochemistry
  • Models, Animal
  • Photoreceptor Cells, Vertebrate/physiology
  • Polymorphism, Restriction Fragment Length
  • Retina/embryology*
  • Retinal Cone Photoreceptor Cells/cytology*
  • Stem Cells/physiology*
  • T-Box Domain Proteins/physiology*
  • Thyroid Hormone Receptors beta/physiology*
  • Zebrafish
  • Zebrafish Proteins/physiology*
(all 19)
PubMed
30592497 Full text @ Invest. Ophthalmol. Vis. Sci.
Abstract
Purpose Replacing cone photoreceptors, the units of the retina necessary for daytime vision, depends upon the successful production of a full variety of new cones from, for example, stem cells. Using genetic experiments in a model organism with high cone diversity, zebrafish, we map the intersecting effects of cone development factors gdf6a, tbx2b, and thrβ.
Methods We investigated these genes of interest by using genetic combinations of mutants, gene knockdown, and dominant negative gene expression, and then quantified cone subtype outcomes (which normally develop in tightly regulated ratios).
Results Gdf6a mutants have reduced blue cones and, discovered here, reduced red cones. In combined gdf6a/tbx2b disruption, the loss of gdf6a in heterozygous tbx2b mutants reduced UV cones. Intriguingly, when we disrupted thrβ in gdf6a mutants by using a thrβ morpholino, their combined early disruption revealed a lamination phenotype. Disrupting thrβ activity via expression of a dominant negative thrβ (dnthrβ) at either early or late retinal development had differential outcomes on red cones (reduced abundance), versus UV and blue cones (increased abundance). By using dnthrβ in gdf6a mutants, we revealed that disrupting thrβ activity did not change gdf6a mutant cone phenotypes.
Conclusions Gdf6a loss directly affects blue and red cones and indirectly affects UV cones by increasing sensitivity to additional disruption, such as reduced tbx2b, resulting in fewer UV cones. The effects of thrβ change through photoreceptor development, first promoting red cones and restricting UV cones, and later restricting UV and blue cones. The effects of gdf6a on UV, blue, and red cone development overlap with, but likely supersede, those of thrβ.
Genes / Markers
Figures
Figure Gallery (4 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
WT + MO2-thrbstandard conditionsDay 4
WT + MO2-thrbstandard conditionsDay 4
WT + MO2-thrbstandard conditionsDay 4
WT + MO2-thrbstandard conditionsDay 4
WT + MO2-thrbstandard conditionsDay 4
WT + MO2-thrbstandard conditionsDay 4
WT + MO2-thrbstandard conditionsDay 4
WT + MO2-thrbstandard conditionsDay 4
gdf6as327/+; tbx2bc144/c144standard conditionsDay 4
gdf6as327/s327standard conditionsDay 4
1 - 10 of 47
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
c144
    		Point Mutation
    kj9TgTransgenic Insertion
      s327
        		Point Mutation
        ua3011TgTransgenic Insertion
          ua3113TgTransgenic Insertion
            1 - 5 of 5
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            Human Disease / Model
            No data available
            Sequence Targeting Reagents
            Fish
            Antibodies
            Orthology
            Engineered Foreign Genes
            Marker Marker Type Name
            EGFPEFGEGFP
            mCherryEFGmCherry
            1 - 2 of 2
            Show
            Mapping
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            Citation
            DuVal, M.G., Allison, W.T. (2018) Photoreceptor Progenitors Depend Upon Coordination of gdf6a, thrβ, and tbx2b to Generate Precise Populations of Cone Photoreceptor Subtypes. Investigative ophthalmology & visual science. 59:6089-6101.