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    Date Issued2009 (1)Author
    Holt, Christine E. (1)
    Huang, Yi-Shuian (1)Lin, Andrew C. (1)Lin, Chien-Ling (1)Richter, Joel D. (1)View MoreUMass Chan AffiliationProgram in Molecular Medicine (1)Document TypeJournal Article (1)KeywordAnimals (1)Axons (1)Base Sequence (1)Cytoplasm (1)Fluorescent Antibody Technique (1)View MoreJournalNeural development (1)

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    Cytoplasmic polyadenylation and cytoplasmic polyadenylation element-dependent mRNA regulation are involved in Xenopus retinal axon development

    Lin, Andrew C.; Tan, Chin Lik; Lin, Chien-Ling; Strochlic, Laure; Huang, Yi-Shuian; Richter, Joel D.; Holt, Christine E. (2009-03-02)
    BACKGROUND: Translation in axons is required for growth cone chemotropic responses to many guidance cues. Although locally synthesized proteins are beginning to be identified, how specific mRNAs are selected for translation remains unclear. Control of poly(A) tail length by cytoplasmic polyadenylation element (CPE) binding protein 1 (CPEB1) is a conserved mechanism for mRNA-specific translational regulation that could be involved in regulating translation in axons. RESULTS: We show that cytoplasmic polyadenylation is required in Xenopus retinal ganglion cell (RGC) growth cones for translation-dependent, but not translation-independent, chemotropic responses in vitro, and that inhibition of CPE binding through dominant-negative interference severely reduces axon outgrowth in vivo. CPEB1 mRNA transcripts are present at low levels in RGCs but, surprisingly, CPEB1 protein was not detected in eye or brain tissue, and CPEB1 loss-of-function does not affect chemotropic responses or pathfinding in vivo. UV cross-linking experiments suggest that CPE-binding proteins other than CPEB1 in the retina regulate retinal axon development. CONCLUSION: These results indicate that cytoplasmic polyadenylation and CPE-mediated translational regulation are involved in retinal axon development, but that CPEB1 may not be the key regulator of polyadenylation in the developing retina.
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