Abstract
Ran-binding protein family member, RanBP9 has been reported in various basic cellular mechanisms and neuropathological conditions including schizophrenia. Previous studies have reported that RanBP9 is highly expressed in the mammalian brain and retina; however, the role of RanBP9 in retinal development is largely unknown. Here, we present the novel and regulatory roles of RanBP9 in retinal development of a vertebrate animal model, zebrafish. Zebrafish embryos exhibited abundant expression of ranbp9 in developing brain tissues as well as in the developing retina. Yeast two-hybrid screening demonstrated the interaction of RanBP9 with Mind bomb, a component of Notch signaling involved in both neurogenesis and neural disease autism. The interaction is further substantiated by co-localization studies in cultured cells. Knockdown of ranbp9 resulted in retinal dysplasia with defective proliferation of retinal cells, downregulation of neuronal differentiation marker huC, elevation of neural proliferation marker her4, and alteration of cell cycle marker p57kip2. Expression of the Müller glial cell marker glutamine synthase was also affected in knockdown morphants. Our results suggest that Mind bomb-binding partner RanBP9 plays a role during retinal cell development of zebrafish embryogenesis.
Keywords:
RanBP9; mind bomb; notch; retinogenesis; zebrafish.
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Animals
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Brain / cytology
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Brain / embryology
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Brain / metabolism
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COS Cells
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Cell Proliferation
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Chlorocebus aethiops
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Cyclin-Dependent Kinase Inhibitor p57 / genetics
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Cyclin-Dependent Kinase Inhibitor p57 / metabolism
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism*
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Down-Regulation
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ELAV-Like Protein 3 / genetics
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ELAV-Like Protein 3 / metabolism
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Ependymoglial Cells / physiology
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Gene Knockdown Techniques
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Neurogenesis / physiology
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Retina / cytology
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Retina / embryology*
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Retina / metabolism
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Retinal Dysplasia / genetics
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Two-Hybrid System Techniques
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Ubiquitin-Protein Ligases / genetics
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Ubiquitin-Protein Ligases / metabolism*
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Zebrafish / embryology*
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Zebrafish / genetics
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Zebrafish / metabolism
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Zebrafish Proteins / genetics
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Zebrafish Proteins / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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Basic Helix-Loop-Helix Transcription Factors
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Cyclin-Dependent Kinase Inhibitor p57
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Cytoskeletal Proteins
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ELAV-Like Protein 3
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Nuclear Proteins
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Ran binding protein 9
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Zebrafish Proteins
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elavl3 protein, zebrafish
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her4.1 protein, zebrafish
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Ubiquitin-Protein Ligases
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mib1 protein, zebrafish