PUBLICATION

Sfrp1a and Sfrp5 function as positive regulators of Wnt and BMP signaling during early retinal development

Authors
Holly, V.L., Widen, S.A., Famulski, J.K., and Waskiewicz, A.J.
ID
ZDB-PUB-140321-26
Date
2014
Source
Developmental Biology   388(2): 192-204 (Journal)
Registered Authors
Waskiewicz, Andrew
Keywords
BMP, Coloboma, Gdf6, Retina, Sfrp1, Sfrp5, Wnt
MeSH Terms
  • In Situ Hybridization
  • Bone Morphogenetic Proteins/metabolism*
  • Signal Transduction*
  • Real-Time Polymerase Chain Reaction
  • Morphogenesis
  • Wnt Proteins/metabolism*
  • Zebrafish
  • Base Sequence
  • Intercellular Signaling Peptides and Proteins/physiology*
  • Zebrafish Proteins/physiology*
  • Animals
  • Retina/embryology*
  • DNA Primers
(all 13)
PubMed
24457098 Full text @ Dev. Biol.
Abstract

Axial patterning of the developing eye is critically important for proper axonal pathfinding as well as for key morphogenetic events, such as closure of the optic fissure. The dorsal retina is initially specified by the actions of Bone Morphogenetic Protein (BMP) signaling, with such identity subsequently maintained by the Wnt-β catenin pathway. Using zebrafish as a model system, we demonstrate that Secreted frizzled-related protein 1a (Sfrp1a) and Sfrp5 work cooperatively to pattern the retina along the dorso-ventral axis. Sfrp1a/5 depleted embryos display a reduction in dorsal marker gene expression that is consistent with defects in BMP- and Wnt-dependent dorsal retina identity. In accord with this finding, we observe a marked reduction in transgenic reporters of BMP and Wnt signaling within the dorsal retina of Sfrp1a/5 depleted embryos. In contrast to studies in which canonical Wnt signaling is blocked, we note an increase in BMP ligand expression in Sfrp1a/5 depleted embryos, a phenotype similar to that seen in embryos with inhibited BMP signaling. Overexpression of a low dose of sfrp5 mRNA causes an increase in dorsal retina marker gene expression. We propose a model in which Sfrp proteins function as facilitators of both BMP and Wnt signaling within the dorsal retina.

Genes / Markers
Figures
Figure Gallery (16 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
mw29TgTransgenic Insertion
    ua1013TgTransgenic Insertion
      w25TgTransgenic Insertion
        w32TgTransgenic Insertion
          1 - 4 of 4
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          gdf6aMO1-gdf6aMRPHLNO
          gdf6aMO5-gdf6aMRPHLNO
          sfrp1aMO1-sfrp1aMRPHLNO
          sfrp1aMO3-sfrp1aMRPHLNO
          sfrp1aMO4-sfrp1aMRPHLNO
          sfrp5MO2-sfrp5MRPHLNO
          sfrp5MO3-sfrp5MRPHLNO
          1 - 7 of 7
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          Fish
          Antibodies
          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          EGFPEFGEGFP
          GFPEFGGFP
          1 - 2 of 2
          Show
          Mapping
          No data available