title: Gdf6a is required for the initiation of dorsal-ventral retinal patterning and lens development.
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.
authors: Department of Biological Sciences, University of Alberta, CW405, Biological Sciences Bldg., Edmonton T6G 2E9, Canada.
authors: Curtis R
authors: CR
authors: French
authors: Timothy
authors: T
authors: Erickson
authors: Danielle V
authors: DV
authors: French
authors: David B
authors: DB
authors: Pilgrim
authors: Andrew J
authors: AJ
authors: Waskiewicz
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000502:physiology; D055415:Bone Morphogenetic Protein 4 / Q000096:biosynthesis / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000502:physiology; D055785:Gene Knockdown Techniques; D055431:Growth Differentiation Factor 6 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007908:Lens, Crystalline / Q000196:embryology* / Q000378:metabolism; D012160:Retina / Q000196:embryology* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051785:Smad Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D020825:T-Box Domain Proteins / Q000235:genetics; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: D055415:Bone Morphogenetic Protein 4; D055431:Growth Differentiation Factor 6; D051785:Smad Proteins; D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5; D029961:Zebrafish Proteins; C525813:bmp4 protein, zebrafish; C420987:gdf6a protein, zebrafish