ZFIN ID: ZDB-PUB-090629-20
Gdf6a is required for the initiation of dorsal-ventral retinal patterning and lens development
French, C.R., Erickson, T., French, D.V., Pilgrim, D.B., and Waskiewicz, A.J.
Date: 2009
Source: Developmental Biology   333(1): 37-47 (Journal)
Registered Authors: Pilgrim, David, Waskiewicz, Andrew
Keywords: Gdf6, Gdf6a, Bmp, Dorsal-ventral patterning, Lens, Retina, Smad, tbx5, vax2
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Body Patterning/physiology
  • Bone Morphogenetic Protein 4/biosynthesis
  • Bone Morphogenetic Protein 4/genetics
  • Embryo, Nonmammalian/physiology
  • Gene Knockdown Techniques
  • Growth Differentiation Factor 6/biosynthesis
  • Growth Differentiation Factor 6/genetics
  • Growth Differentiation Factor 6/physiology*
  • Lens, Crystalline/embryology*
  • Lens, Crystalline/metabolism
  • Retina/embryology*
  • Retina/metabolism
  • Signal Transduction/physiology
  • Smad Proteins/antagonists & inhibitors
  • Smad Proteins/physiology
  • T-Box Domain Proteins/genetics
  • Zebrafish
  • Zebrafish Proteins/biosynthesis
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
PubMed: 19545559 Full text @ Dev. Biol.
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ABSTRACT
Dorsal-ventral patterning of the vertebrate retina is essential for accurate topographic mapping of retinal ganglion cell (RGC) axons to visual processing centers. Bone morphogenetic protein (Bmp) growth factors regulate dorsal retinal identity in vertebrate models, but the developmental timing of this signaling and the relative roles of individual Bmps remain unclear. In this study, we investigate the functions of two zebrafish Bmps, Gdf6a and Bmp4, during initiation of dorsal retinal identity, and subsequently during lens differentiation. Knockdown of zebrafish Gdf6a blocks initiation of retinal Smad phosphorylation and dorsal marker expression, while knockdown of Bmp4 produces no discernable retinal phenotype. These data, combined with analyses of embryos ectopically expressing Bmps, demonstrate that Gdf6a is necessary and sufficient for initiation of dorsal retinal identity. We note a profound expansion of ventral retinal identity in gdf6a morphants, demonstrating that dorsal BMP signaling antagonizes ventral marker expression. Finally, we demonstrate a role for Gdf6a in non-neural ocular tissues. Knockdown of Gdf6a leads to defects in lens-specific gene expression, and when combined with Bmp signaling inhibitors, disrupts lens fiber cell differentiation. Taken together, these data indicate that Gdf6a initiates dorsal retinal patterning independent of Bmp4, and regulates lens differentiation.
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