Abstract
Visual system development is dependent on correct interpretation of cues that direct growth cone migration and axon branching. Mutations in the zebrafish esrom gene disrupt bundling and targeting of retinal axons, and also cause ectopic arborization. By positional cloning, we establish that esrom encodes a very large protein orthologous to PAM (protein associated with Myc)/Highwire/RPM-1. Unlike motoneurons in Drosophila highwire mutants, retinal axons in esrom mutants do not arborize excessively, indicating that Esrom has different functions in the vertebrate visual system. We show here that Esrom has E3 ligase activity and modulates the amount of phosphorylated Tuberin, a tumor suppressor, in growth cones. These data identify a mediator of signal transduction in retinal growth cones, which is required for topographic map formation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / biosynthesis*
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Adaptor Proteins, Signal Transducing / genetics*
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Adaptor Proteins, Signal Transducing / physiology*
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Animals
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Axons / physiology*
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Chromosome Mapping
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Cloning, Molecular
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Drosophila
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Eye / embryology*
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Genotype
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Growth Cones / metabolism*
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In Situ Hybridization
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Ligands
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Microscopy, Fluorescence
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Mixed Function Oxygenases / biosynthesis*
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Mixed Function Oxygenases / genetics*
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Mixed Function Oxygenases / physiology*
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Models, Biological
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Models, Genetic
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Phenotype
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Phosphorylation
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RNA / metabolism
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Repressor Proteins / biosynthesis
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Retina / embryology*
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Retina / metabolism
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Signal Transduction
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Transgenes
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Tuberous Sclerosis Complex 2 Protein
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Tumor Suppressor Proteins
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Ubiquitin-Protein Ligases / metabolism
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Zebrafish
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Zebrafish Proteins / biosynthesis*
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Zebrafish Proteins / genetics*
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Zebrafish Proteins / physiology
Substances
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Adaptor Proteins, Signal Transducing
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Ligands
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Repressor Proteins
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TSC2 protein, human
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Tuberous Sclerosis Complex 2 Protein
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Tumor Suppressor Proteins
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Zebrafish Proteins
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mycbp2 protein, zebrafish
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RNA
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Mixed Function Oxygenases
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MYCBP2 protein, human
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Ubiquitin-Protein Ligases